Tropical Journal of Pharmaceutical Research

Evaluation of diclofenac emulgel prepared with sesame oil as a lipophilic carrier

Zwanden Sule Yahaya — 2023-11-06

Purpose: To investigate the suitability of sesame oil as an oily phase for diclofenac emulgel formulation.

Methods: Different batches of emulgel comprising different proportions of oils (sesame oil and/or Labrafac CC), surfactants (Tween-80 and/or cremophor EL-30), and gelling agents (xanthan gum or gelatin) were prepared. The formulations were evaluated for rheology, syneresis, Fourier transform infrared (FTIR) spectroscopy, spreadability, extrudability, and anti-inflammatory activity.

Results: Product characteristics of batches A2, A4, and A6 were not consistent with those of emulgels. Because Batch A1 showed characteristics that were the most stable, such as no pH changes, nonstatistically significant changes (p = 1.000) in the viscosity results, and least spectrum changes following FTIR investigation, it was selected as the best batch. It showed similar anti-inflammatory activity when compared with commercially available diclofenac emulgel, giving a 50 % higher anti-inflammatory effect than aqueous diclofenac dispersion.

Conclusion: Sesame oil is a potential lipophilic component in emulgel formulations for topical delivery of hydrophobic drugs.

Co-delivery of combretastatin A4 and docetaxel with pegylated nanostructured lipid carriers in tumor cells

Caifeng Jia — 2023-11-06

Purpose: To investigate a novel co-delivery system using nanostructured lipid carriers (NLCs) for simultaneous administration of two potent anti-cancer drugs, combretastatin A-4 (CA-4) and docetaxel (DTX), against tumor cells and vasculature.

Methods: The CA-4 and DTX co-loaded NLCs (C-D-NLC) were formulated and investigated for physical properties, stability, and drug release. Safety and efficacy of C-D-NLC were investigated on Lewis Lung Carcinoma (LLC) tumor cells in vitro and in vivo using cytotoxicity and anti-tumor assays. The pharmacokinetics of CA-4 and DTX in rats after intravenous injection of C-D-NLC were also studied to evaluate potential drug interactions.

Results: The C-D-NLC was successfully prepared with a spherical shape, mean size of 130 nm, negative charge, high encapsulation efficiency and drug loading of 94.89, 88.16, 2.44, and 4.52 for DTX and CA-4, respectively. Also, C-D-NLC had a significant inhibitory effect on LLC cells, superior to a single drug or solution group. Combretastatin A4 did not affect the pharmacokinetics of DTX, but combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) reduced plasma clearance of CA-4 and DTX, prolonged half-life, mean residence time, and increased area under concentration curves (AUC) values. Furthermore, combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) inhibited the growth of LLC tumors in mice and reduced drug toxicity.

Conclusion: Combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) sustain drug release and enhance tumor growth inhibition of CA-4 and DTX by targeting both tumor cells and vasculature. The co-delivery system prolongs drug circulation compared to solution administration. Thus, nanostructured lipid carriers (NLCs) with dual drug loading may be a promising strategy for clinical combination chemotherapy in future.

CircPDSS1 accelerates malignant progression of renal cell carcinoma through sponging of miR-182-5p

Jia Wang — 2023-11-06

Purpose: To investigate the biological function and mechanisms of circPDSS1 in triggering malignant progression of renal cell carcinoma (RCC).

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine circPDSS1 levels in 50 pairs of RCC and para-cancerous tissues. The relationship between circPDSS1 level and pathological indices in RCC patients was analyzed, while the in vitro effect of circPDSS1 in regulating RCC proliferation was assessed using cell counting kit-8 (CCK-8), colony formation and 5- ethynyl-2’- deoxyuridine (EdU) assay. The sponge effect of circPDSS1 on miR-182-5p was examined by bioinformatics analysis and dual- luciferase reporter assay, while their involvement in mediating malignant progression of RCC was analyzed using rescue experiments. In vivo, the influence of circPDSS1 on RCC growth was determined by establishing a xenograft model in nude mice. Thereafter, RCC tissues were harvested from mice to assess relative levels of miR-182-5p and Ki-67.

Results: CircPDSS1 was highly expressed in RCC tissues (p < 0.05). A high level of circPDSS1 correlated with advanced tumor staging and low overall survival. Knockdown of circPDSS1 inhibited RCC cell proliferation, and CircPDSS1 sponged and negatively regulated miR-182-5p (p < 0.05). MiR182-5p was able to abolish regulatory effect of circPDSS1 on malignant proliferative potential in RCC cells. In nude mice bearing RCC, in vivo knockdown of circPDSS1 slowed down tumor growth and decreased positive expression of Ki-67 in tumor tissues (p < 0.05).

Conclusion: CircPDSS1 predicts tumor stage and prognosis in RCC patients. It triggers malignant progression of RCC through sponging of miR-182-5p.

Hederagenin inhibits proliferation, angiogenesis and inflammation of fibroblast-like synovial cells in rheumatoid arthritis

Ping Wang — 2023-11-06

Purpose: To determine the effect of Hederagenin (Hed) on rheumatoid arthritis (RA) in a cell model, and to elucidate the mechanism of action of Hed.

Methods: MTT, EDU, and Immunoblot assays were used to determine the effects of Hed on the viability of fibroblast-like synovial cells, while the effects of Hed on inflammation were examined by enzymelinked immunosorbent assay (ELISA) and immunoblot assay. The influence of Hed on cell motility angiogenesis was evaluated by Transwell and tube formation assays, while immunoblot analysis was used to determine the mechanism of action of Hed.

Results: Hed inhibited the viability of RA-FLS cells and suppressed the inflammation of RA-FLS cells (p < 0.05). Furthermore, Hed suppressed the migration and angiogenesis of RA-FLSl cells, as well as regulated MAPK pathway (p < 0.05).

Conclusion: Hed inhibits the proliferation, angiogenesis and inflammation of fibroblast-like synovial cells in RA by regulating MAPK pathway. Therefore, Hed is a drug for the treatment of RA, However, in vivo studies to validate these findings are recommended

Oxaliplatin regulates the autophagy of skin squamous cell carcinoma cell line through HMGB1 pathway

Lei Han — 2023-11-06

Purpose: To determine the influence of oxaliplatin on skin squamous cell carcinoma cell line, and the involvement of autophagy- regulating pathway of high mobility group box 1 (HMGB1) in the process.

Methods: A431 cells cultured in vitro were used. The cells were divided into groups A (treated with different concentrations of oxaliplatin) and B (treated with different concentrations of oxaliplatin combined with autophagy inhibitor 5 mmol/l3-ma). Changes in expression levels of autophagy marker molecules LC3-Ⅰ, LC3-Ⅱ, p62 and HMGB1 in A431 cells treated with different concentrations of oxaliplatin and different concentrations of HMGB1 were evaluated by Western blotting. Viability of A431 cells in both groups was assessed by CCK-8 assay.

Results: With increase in oxaliplatin concentration, LC3-Ⅱ levels in A431 cells were up-regulated, p62 expression decreased, while autophagy level was increased significantly (p < 0.05). With increase in HMGB1 protein concentration, LC3-Ⅱ level in A431 cells was raised, while p62 level was reduced, while the level of autophagy was significantly increased (p < 0.05). Oxaliplatin treatment led to significantly higher expression level of HMGB1 in the experimental group than in the control group without oxaliplatin treatment. The viability of oxaliplatin-treated group was dose-dependently and significantly lower (p < 0.05) than that of the control group. Compared with the control group, the cell viability of the 3-mA + oxaliplatin group also showed a downward trend, and the decrease was greater than that of oxaliplatin-treated group (p < 0.05).

Conclusion: Oxaliplatin upregulates autophagy by promoting HMGB1 protein expression, which may be a protective mechanism of tumor cells against oxaliplatin cytotoxicity thereby making HMGB1 protein a potential target in skin cancer therapy.

Effect of miR-138 on migration and invasion of cervical cancer cells, and the underlying mechanism

Yanxi Li — 2023-11-06

Purpose: To study the influence of microRNA-138 (miR-138) on the migration and invasion of cervical cancer cells, and the underlying mechanism.

Methods: Fifteen cervical carcinoma subjects were enrolled in the study. Control group comprised cervical epithelial cell line (End1/E6E7) while cervical cancer group was human cervical squamous cell carcinoma cell line c33a. Both were cultured routinely without any treatment. In miR-138 overexpression group, cells were cultured in progeny of human cervical squamous carcinoma cell line c33a infected with miR-138 gene overexpression lentivirus. Expression levels of miR-138 in excised cervical cancer tissues were determined using qPCR. Cell proliferation was determined with CCK8 assay. Immunoblotting was utilized to assay protein expression levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine mRNA expression levels, while cell migration and invasion were assessed by Transwell method.

Results: There was significant down-regulation of miR-138 expression in cervical cancer tissue, relative to nearby tissues (p < 0.05). In miR-138 overexpression group, cell proliferation, number of migrated and invaded cells were significantly reduced, relative to corresponding levels in cervical cancer cells. There were significantly higher expression levels of apoptosis-related proteins FAS, Bax and FasL in miR-138 overexpression group than in cervical cancer cells, while Bcl-2 was significantly downregulated, relative to cervical cancer group (p < 0.05). In cervical cancer cells, mRNA and protein levels of SIRT1 and HIF-1α were significantly up-regulated, relative to corresponding control, but levels of HIF1α and miR-138 were significantly reduced in overexpression group when compared to cervical cancer group (p < 0.05).

Conclusion: Up-regulating miR-138 in cervical cancer cells reduces HIF-1α through inhibition of SIRT1 signaling, resulting in suppression of multiplication, migration and invasion of cervical cancer cells, while enhancing apoptotic changes.

Identification of potential biomarkers and candidate smallmolecule drugs for heart failure via comprehensive gene microarray analysis

Hailang Liu — 2023-11-06

Purpose: To identify potential novel biomarkers and to explore new small-molecule drugs for heart failure (HF).

Methods: The Gene Expression Omnibus (GEO) microarray datasets were downloaded for analyzing the differentially expressed genes (DEGs). Venn analysis was performed to calculate the overlapping genes which were then used for Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using cluster Profiler in R package; a protein-protein interaction network (PPI) was constructed using STRING database. The hub genes were selected for small-molecule drug identification, while molecular docking of small-molecule drugs and hub genes was performed using CBdock2.

Results: Upregulated and downregulated DEGs were obtained from GSE84796, GSE107569 and GSE116250 datasets, respectively. Eleven (11) overlapping genes, which were enriched in collagen fiber tissue, collagen-containing extracellular matrix and collagen fiber-related pathways, were also enriched in AGE-RAGE and relaxin signaling pathways. The PPI network of the DEGs was constructed, and five hub genes, with high connectivity, were significantly upregulated in HF. The five hub genes were ranked as MFAP4, LTBP2, THBS4, COL3A1 and COL1A1. Two targets (COL1A1 and COL3A1) matched potential drugs, and fostamatinib shared by the two targets had the greatest therapeutic value for HF.

Conclusion: Five novel biomarkers and involved signaling pathways have been identified in HF via comprehensive microarray analyses. The results also show that fostamatinib might be a promising drug candidate for HF treatment

Tectorigenin functions as a potential drug for melanoma treatment via inhibition of cell growth, migration and aerobic glycolysis

Qiao Yan — 2023-11-06

Purpose: To investigate the role of tectorigenin (TG) in melanoma cells.

Methods: Viability of A375 and A2058 melanoma cells was determined by cell counting kit (CCK-8) assay. Cell cycle progression was analyzed by 5-ethynyl-2’-deoxyuridine (EdU) staining. Migration and invasion of melanoma cells were determined by Transwell assay. The epithelial-mesenchymal transition (EMT) of melanoma cells was investigated by determining expression of E-Cadherin and Snail. Expression of glucose transporter 1 (GLUT1) and lactose dehydrogenase A (LDHA) was assessed via western blotting. Glucose and lactate production was evaluated by corresponding assay kit. The NOX4 and FOXM1 expressions were determined using western blotting.

Results: Tectorigenin inhibited proliferation, migration and invasion of A375 and A2058 melanoma cells. Tectorigenin regulated cell cycle progression by decreasing the number of cells in S-phase and significantly inhibited snail expression and increased expression of E-Cadherin (p < 0.05), thus inhibiting the EMT of A375 and A2058 cells. Tectorigenin inhibited expression of GLUT1 and LDHA, thereby leading to reduction in glucose consumption and lactate production. It also significantly inhibited expressions of NOX4 and FOXM1 (p < 0.05), indicating an inhibitory effect on the activity of NOX4/FOXM1 pathway.

Conclusion: Tectorigenin inhibits aerobic glycolysis, growth and migration in melanoma cells by suppressing the activity of NOX4/FOXM1 pathway, suggesting its potential in melanoma treatment.

MiR-22 inhibits angiotensin II-induced aortic dissection and protects aortic vessel wall in mice by targeting MAPK14

Xinming Yu — 2023-11-06

Purpose: To study the effect of miR-22 on angiotensin II-induced aortic dissection in mice, and its protective effect on aortic vessel wall, as well the involvement of MAPK-14 in these processes.

Methods: A mouse aortic dissection model was established via subcutaneous implantation of angiotensin II (1 µg/kg/min) micropump in the dorsal region. The mice (n = 30) were assigned in equal numbers to 5 groups (n = 6). All injections were given via the tail vein. The miR-22 expressions in aortas of mice in each group were determined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot assay was used to determine the expressions of MAPK-14 protein, while H&E staining was used to measure the ratio of aortic thickness-to-diameter, and contents of collagen and elastic fibers.

Results: The expression of miR-22 in aorta of mice in miR-22 overexpression group was significantly higher than that in overexpression control group, but significantly lower in miR-22 inhibition mouse than in inhibition control mouse (p < 0.05). There was significantly lower protein expression of MAPK-14 in mice aorta in miR-22 overexpression mice than in overexpression control mice, but significantly upregulated in miR-22 inhibition mice, relative to that in inhibition control mice (p < 0.05). In the miR-22 overexpression mice, the ratio of membrane thickness-to-diameter was higher than the corresponding value in miR-22 inhibition mice. There were significantly higher contents of aortic elastic and collagen fibers in miR-22 overexpression mice than in overexpression control and miR-22 inhibition groups (p < 0.05).

Conclusion: Overexpression of miR-22 inhibits the up-regulation of expression of its target gene mapk14, increases thickness of aortic media and aortic elasticity in mice, and increase the content of collagen fibers, thereby exerting protective effect on aortic wall structure.

Effect of gold nanocomposite bearing HIF-1α siRNA on radiotherapy in nasopharyngeal carcinoma cell

Haosheng Zhang — 2023-11-06

Purpose: To investigate the effect of gold nanocomposite carrying hypoxia-inducible factor-1α (HIF-1α) siRNA on radiosensitivity of nasopharynx cancer (NPC) cells.

Methods: Gold nanocomposite (AuNRs-(PEI-PEG)/RGD) or (AuPPR) was first synthesized and its cytotoxicity was evaluated. Then, the expression of HIF-1α in hypoxic NPC cells was assessed. In addition, the radiation sensitivity of AuPPR bearing HIF-1α siRNA on the cells was examined under xray exposure.

Result: Gold nanocomposite (AuPPR) carrying HIF-1α siRNA (AuPPR-HIF-1α siRNA) significantly down-regulated HIF-1α expression. Under irradiation treatment, AuPPR-HIF-1α siRNA significantly enhanced apoptosis of NPC cells by 33.76 ± 3.65 %, when compared to the control and simple AuPPR group (22.5 ± 4.16 %, p < 0.01). Furthermore, cell cycle was significantly blocked in the sub-G1 phase in AuPPR-HIF-1α siRNA radiotherapy groups, indicating severe cell damage.

Conclusion: This study has demonstrated that AuPPR-HIF-1α siRNA is effective in improving the radiosensitivity of nasopharyngeal carcinoma cells under hypoxia, and therefore can potentially be used to improve the radiotherapy of this carcinoma

Effect of 20-hydroxyecdysone and its metabolites in the absence or presence of IGF-1 on regulation of skeletal muscle cell growth

Kanokwan Suhatcho — 2023-11-06

Purpose: To investigate the effect of 20-hydroxyecdysone (20E) and its metabolites and their synergistic effect with IGF-1 on regulation of skeletal muscle cell growth.

Methods: Mouse skeletal muscle cell line (C2C12) was solely treated with 20E and its metabolites (14- deoxy- 20-hydroxyecdysone, poststerone, and 14-deoxypoststerone) at doses of 0.1, 1, and 10 µM or co-treated with IGF-1 (10 ng/ml). Cell viability and proliferative capacity were evaluated using MTT and BrdU incorporation assays, respectively. Myogenic differentiation proteins [embryonic myosin heavy chain (EbMHC) and MHC], androgen receptor (AR), and IGF-1 receptor (IGF-1R) protein expression were investigated using immunocytochemistry.

Results: Treatments of 20E and its metabolites had no toxicity on skeletal muscle cells or induced AR/IGF-1R expression. In addition, solely treatment of 20E and its metabolites or co-treatment with IGF-1 had no significant effect on cell proliferation and myogenic differentiation capacity. In contrast, IGF-1 treatment alone significantly increased EbMHC expression (p<0.0001), MHC expression (p<0.05), and myotube number (p<0.05).

Conclusion: These results indicate that 20E and its metabolites have no direct or synergistic effect with IGF-1 on skeletal muscle cell growth. Nevertheless, the pharmacological effects of 20E on skeletal muscle mass and strength in vivo that raises its therapeutic potential may associate with its indirect action.

Alkaloids from Peganum harmala attenuated contractile responses of vascular smooth muscle cells

Mohamed K. Al-Essa — 2023-11-06

Purpose: To investigate the contractile responses of vascular smooth muscle cells (VSMCs) to spasmogens after incubation with harmaline, harmine, and harmalol, which are alkaloids obtained from Peganum harmala L., a member of the Zygophyllaceae family.

Methods: Contractile responses of VSMCs to norepinephrine (NE; 1 µmol/L) and potassium chloride (KCl; 60 mmol/L) were recorded in rat aortic ring preparations pre-incubated with 0.5, 1, 5 and 10 µmol/L of each alkaloid for 15 min. Responses were expressed as mean values of contractions in incubated preparations, relative to the recorded tension prior to treatment with alkaloids.

Results: Pre- incubation with harmaline at concentration of 10 µmol/L significantly reduced contractile responses to NE by 69.0 ± 3.0 % (p < 0.00002), and decreased KCl-induced contraction by 34.0 ± 9.0 % (p < 0.05). Harmalol was the most effective in inhibiting contractions to KCl (48.0 ± 9.0 %, p < 0.01). However, harmalol produced relatively moderate inhibitory effects on NE-induced contractions (46.0 ± 4.0 %, p < 0.005), followed by harmine (52.0 ± 8.0 %, p < 0.02), but it did not significantly affect contractile responses to KCl.

Conclusion: These results highlight the differential effects of pre-incubation with alkaloids from P. harmala and their potential effects on the prevention of VSMC spasms induced by either chemicals or stimuli that change the membrane potential.

Effect of paclitaxel octreotide conjugate on human ovarian paclitaxel-resistant cell xenograft tumor model and the mechanism underlying reversal of paclitaxel resistance

Hui Guo — 2023-11-06

Purpose: To determine the effect of paclitaxel octreotide conjugate (POC) on human ovarian paclitaxelresistant cell xenograft tumor model and the mechanism underlying reversal of paclitaxel resistance.

Methods: Forty female BALB/c-nu/nu mice were subcutaneously inoculated with 106 paclitaxel-resistant cells (a2780/taxol) per mouse during the logarithmic growth phase of ovarian cancer. They were randomly divided into four groups (control, octreotide, paclitaxel and POC). Immunohistochemical streptavidin-peroxidase (SP) method was used to determine expression of nuclear proliferation antigen (PCNA) while TUNEL method was used to assess apoptosis of human ovarian cancer metastasis. Realtime polymerase chain reaction (PCR) was used to assay mRNA expression levels of somatostatin receptor 2 (SSTR2), multidrug-resistant gene (MDR1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and acetylated tubulin (α-tubulin and β-III-tubulin), while the corresponding protein expressions were assayed using western blotting.

Results: Immunohistochemical SP showed significantly lower PCNA levels in octreotide, paclitaxel and POC groups than in control mice, but that of POC mice was significantly reduced, relative to those of octreotide and paclitaxel groups (p < 0.05). There were significantly higher expression levels of SSTR2 mRNA and protein in octreotide, paclitaxel and POC groups than in control mice, but they were significantly higher in POC group than in octreotide and paclitaxel groups (p < 0.05). The mRNA and protein expressions of other factors in POC mice were significantly lower than those in both octreotide and paclitaxel groups (p < 0.05).

Conclusion: Paclitaxel-octreotide conjugate effectively inhibits the growth of a2780/taxol xenografts in nude mice, induces tumor cell apoptosis, and suppresses tumor cell growth via mechanism involving enhancement of SSTR2 expression, and decreases in levels of acetylated tubulin, matrix metalloproteinase-9, and vascular endothelial growth factor.

Ozone exposure induces cough hypersensitivity in mice

Tinglei Li — 2023-11-06

Purpose: To study the influence of O₃ exposure on cough sensitivity, airway barrier function and airway inflammation in mice.

Methods: Cough sensitivity was determined in healthy male C57/BL6 mice (aged 8 - 10 weeks) which were exposed to different concentrations of O₃ (0.5 - 2 ppm) for 3 h daily for 9 days. Hematoxylin and eosin (H&E) staining of lung tissues, collection of BALF, and cell count were carried out. Inflammatory factor levels in pulmonary tissues were determined by enzyme-linked immunosorbent assay (ELISA), while Western blotting was used to assay TRPA1 and Claudin-1 protein expressions in lung tissues.

Results: After 9 days of mice exposure to O₃, cough sensitivity increased significantly, and TRPA1 protein was increased in pulmonary tissues, with exposure level of 1 ppm resulting in the highest level of TRPA1 protein expression. Claudin-1 expression in lung tissues of mice decreased after O₃ exposure, especially in the groups exposed to O3 levels of 0.5 ppm and 2 ppm. The total cell count in alveolar lavage fluid of mice exposed to O₃ was significantly increased (p < 0.05). In addition, O₃ exposure increased IL-1α, IL-6 and TNF-α levels, with the most significant increase in the 0.5 ppm group (p < 0.05). Results from histology revealed that all mice had inflammatory reactions and destruction of lung tissues after O₃ exposure.

Conclusion: Exposure to O₃ induces disruption of airway barrier function, infiltration of the airway by inflammatory cells, and increased secretion of inflammatory factors, thereby resulting in enhanced cough sensitivity.

Isolation, characterization, structural elucidation and in vivo hepatoprotective studies of phytoconstituents obtained from the fruits of Cordia obliqua Willd

G. Tharun Babu — 2023-11-06

Purpose: To isolate, characterize, and investigate the hepatoprotective effect of phyto-constituents from fruits of Cordia obliqua Wild in paracetamol-induced hepatotoxicity in Wistar rats.

Methods: Ethanol and aqueous extracts of C. obliqua fruits were screened for phytochemicals. The extracts were subjected to column chromatography and preparative thin-layer chromatography (TLC) to isolate four novel compounds. Compounds were characterized using infrared spectroscopy (IR), mass spectroscopy (MS), as well as 1H and 13C nuclear magnetic resonance (NMR). The isolated compounds were assessed for acute toxicity, in vivo hepatoprotective and antioxidant potential (dose: 5 mg/kg) in paracetamol-induced (75 mg/kg) hepatotoxicity through oral route in Wistar rats.

Results: Phytochemical analysis of ethanol (COE) indicated the presence of fatty acids, anthraquinones, glycosides, saponins, alkaloids, tannins, flavonoids, coumarins, phenolics, triterpenes, and sterols. Compounds A, B, and C were identified from COE. Treatment at 50 mg/kg significantly reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGTP), and total bilirubin (TB), as well as increased total protein and total alkalinity levels in serum compared to the positive control. Liver histo-architecture showed improvements compared to the positive control, indicating hepatic protection.

Conclusion: The isolated compounds (A, B and C) from COE exhibit hepatoprotective effects attributed to flavonoids and phenolics with free radical scavenging properties. Further research is needed to identify key mechanisms responsible for hepatoprotective effects.

Efficacy of phentolamine combined with milrinone on severe pneumonia in children, and its effect on serum levels of MMP-9, TIMP-1 and sICAM-1

Jianbiao Chen — 2023-11-06

Purpose: To investigate the effect of the co-administration of phentolamine and milrinone on severe pneumonia in children, as well as on serum MMP-9, TIMP-1 and sICAM-1 levels.

Methods: From January 2021 to January 2022, 100 patients diagnosed with severe pneumonia were randomly divided into 2 groups; the control group received oxygen inhalation and other symptomatic treatment, while the study group received phentolamine concurrently with milrinone, Serum MMP-9, TIMP-1, sICAM-1 levels and clinical efficacy were determined in the two groups before and after treatment.

Results: After treatment, there were significant differences in IL-6, IL-10, and TNF-α levels between the study group and the control group. Furthermore, IgA, IgG, and IgM levels in both groups were significantly higher after treatment than before treatment (p < 0.05). The study group exhibited significant differences in MMP-9, TIMP-1, and sICAM-1 levels after treatment compared to control group (p < 0.05). Healing and therapeutic effectiveness in the study group was 76 %, which was significantly greater than in the control group (48 %; p = 0.000). Additionally, total treatment effectiveness in the study group was 92 %, which was significantly higher than in the control group (80 %; p = 0.015). After treatment, the PEF, FRC, and TEF25 % in the study group were significantly higher than in the control group (p < 0.05).

Conclusion: Co-administration of phentolamine and milrinone is highly effective for the treatment of severe pneumonia in children, and significantly reduces the levels of serum MMP-9, TIMP-1 and sICAM-1. However, multi-center clinical trials should be carried out prior to the adoption of this treatment mode in clinical practice.

Efficacy of the combination of minocycline and periodontal basic therapy in type 2 diabetes mellitus patients with chronic periodontitis

Chuizhuang Chen — 2023-11-06

Purpose: To investigate the clinical efficacy of the combination of minocycline and periodontal basic treatment on type 2 diabetes mellitus (T2DM) patients with chronic periodontitis (CP) and its impact on inflammatory factors.

Methods: A total of 90 T2DM patients with CP admitted to the Department of Stomatology in Hainan Medical College Second Affiliated Hospital, China from January 2020 to October 2022, were enrolled in this study and randomly assigned to two equal groups, viz, study and control group. Study group received minocycline in addition to routine hypoglycemic control and basic periodontal treatment, while control group received only routine hypoglycemic control and basic periodontal treatment. Treatment lasted for 8 weeks. Efficacy of the combination of minocycline and periodontal basic treatment of T2DM patients with CP in the two groups, as well as the periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (sulcus bleeding index, SBI), interleukin-36 (IL-36), interleukin-1β (IL1β), tumor necrosis factor-α (TNF-α), glycated hemoglobin (HbA1c) level, chewing function score, Oral Health Impact Profile-14 (OHIP-14) score, and incidence of adverse reactions before and after treatment were determined.

Results: The effectiveness/efficacy of treatment in study group (91.11 %) was significantly higher than in control group (75.56 %, p < 0.05). After treatment, study group had reduced PD, PLI, and SBI scores than control group (p < 0.05). Study group also showed lower levels of IL-1β, IL-36, and TNF-α as well as reduced OHIP-14 score and a higher chewing function score than control group (p < 0.05).

Conclusion: The combination of minocycline with periodontal basic treatment improves the efficacy in T2DM patients with CP, and reduces the level of inflammatory factors with a good margin of safety.

Efficacy of diquafosol sodium combined with M22 optimized pulsed light in the treatment of dry eye due to meibomian gland dysfunction

Xiaodan Huang — 2023-11-06

Purpose: To determine the efficacy and safety of 3 % diquafosol sodium combined with M22 optimized pulse light (OPT) in the treatment of dry eye due to meibomian gland dysfunction (MGD).

Methods: Data from 97 dry eye patients admitted to Shantou Balder Eye Hospital with MGD-induced dry eye illness between August 2019 and June 2021 were retrospectively reviewed and analyzed. Patients meeting MGD diagnostic criteria in ophthalmology and exhibiting MGD-induced dry eye signs were split into two groups. The medication group (43 cases) received 3 % diquafosol sodium eye drops six times a day for three months, while the pulsed light group (44 cases) underwent three M22 OPT sessions at one-month intervals. Treatment efficacy of the two methods were compared by assessing changes in ocular surface, symptom severity, inflammatory factors (hs-CRP, IL-8, IL-1β), and quality of life before and three months after treatment commenced. Adverse reactions were also recorded.

Results: Pulsed light group showed a slightly higher (but not significant) total effective rate (95.45 %) than the medication group (93.02 %; p > 0.05). Three months post-treatment, both groups exhibited significant improvements in various indicators such as FL, OSDI, symptom scores, tear biomarker levels, and overall eye health (p < 0.05). The incidence of adverse reactions was similar between the medication (4.65 %) and pulsed light (9.09 %) groups.

Conclusion: Treatment with 3 % diquafosol sodium and M22 OPT for MGD-induced dry eye yields comparable efficacy and safety, improving symptoms, ocular surface function, reducing inflammation, and enhancing quality of life. However, 3 % diquafosol sodium shows better patient tolerance and fewer adverse reactions, but further research is needed due to the limited number of patients in this study.

Therapeutic effect of cisatracurium in patients with acute respiratory distress syndrome

Yanping Li — 2023-11-06

Purpose: To investigate the therapeutic effect of cisatracurium, (a neuromuscular blocking agent) in the treatment of acute respiratory distress syndrome (ARDS).

Methods: A total of 94 ARDS patients admitted to The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture ICU from March 2020 to December 2021 were randomly assigned to study and control groups (47 patients each). Both groups received mechanical ventilation, but the study group also received continuous intravenous cisatracurium for 48 h. Health parameters, such as blood gas levels, respiratory mechanics, duration of stay in intensive care unit ICU), mortality rate, and the occurrence of complications, were monitored at 3, 6, and 12 months after treatment.

Results: The study group showed significant improvements compared to control group. Study group also had reduced duration of mechanical ventilation, duration of ICU stay, ICU mortality rate, and incidence of complications (p < 0.05). There were no significant differences in pre-treatment health parameters, but post-treatment, study group had significantly higher levels of blood gas levels and improved lung function (p < 0.05). Study group also had lower scores of illness severity and reduced total mortality rate at 3, 6, and 12 months (p < 0.05).

Conclusion: Administering cisatracurium reduces mechanical ventilation, duration of ICU stay and mortality rate, as well as improves lung function in ARDS patients. Future research involving larger sample size, and takes into consideration regional/environmental differences, is required to validate these findings for reliability.

Safety and efficacy of salvianolate injection in preventing deep vein thrombosis after total hip replacement

Xiaoning Liu — 2023-11-06

Purpose: To investigate the safety and efficacy of salvianolate injection in preventing deep vein thrombosis (DVT) following total hip replacement.

Methods: A total of 114 patients who underwent total hip replacement at Department of Trauma, Fengfeng General Hospital of North China Medical and Health Group, Handan City, China from March 2019 to March 2022 were enrolled. Patients were randomly divided into study group (n = 57) and control group (n = 57). The control group received conventional treatment (low molecular weight heparin) while the study group was administered salvianolate injection combined with conventional treatment. Incidence of deep vein thrombosis (DVT) at 7 and 14 days after surgery, platelet function indices, including platelet count, glycoprotein Ⅱb/Ⅲa (GPⅡb/Ⅲa), and CD62P, coagulation function indices (prothrombin time (PT), fibrinogen (FIB) and D-dimer), and hemodynamics indices, viz, peak blood flow velocity (Vp) and average velocity (Va) were investigated and compared.

Results: Incidence of DVT was 1.75 % (1/57) at 7 days and 5.26 % (3/57) at 14 days in the study group, and 5.26 % (3/57) at 7 days and 17.54 % (10/57) at 14 days in control group. Incidence of DVT in the study group was significantly reduced compared to control group 14 days after surgery (p < 0.05). Also, the study group had significantly lower visual analog scale (VAS) scores at 7 days and 1 month after surgery compared to control group (p < 0.05). Platelet count, GPⅡb/Ⅲa, and CD62P in the study group were significantly lower than in control group (p < 0.05).

Conclusion: Salvianolate injection significantly prevents DVT after total hip replacement, improves hemodynamics, and coagulation function, and thus contributes to recovery of hip function. Further clinical trials are, however, required to validate these findings.

Preliminary study on the relationship between recurrence and quasispecies characteristics in P region of hepatitis B virus genome of chronic hepatitis B patients treated with lamivudine

Baojian Wang — 2023-11-06

Purpose: To investigate the characteristics of quasispecies in the P region of hepatitis B viral (HBV) DNA of chronic hepatitis B (CHB) patients treated with lamivudine (LAM), and its effect on HBV relapse after drug withdrawal in CHB patients who met drug cessation criteria.

Methods: A total of 43 patients with chronic HBV infection, who had undergone LAM therapy, were enrolled in this study. Treatment was discontinued for patients who met therapeutic criteria set by relevant Asian-Pacific regions. Polymerase chain reaction (PCR) was used to amplify the genome in P region of serum rcDNA before treatment, cccDNA during drug cessation period, and serum rcDNA at relapse. Quasispecies cloning and sequencing were performed to identify variable sites in HBV P region.

Results: Mutations in P region of baseline serum rcDNA were detected in 30 CHB patients, with N/H238T (14/30), L/F/Q/R267H (12/30), V278T (12/30), D134E/I (11/30), and T222A (9/30) having highest rates. In hepatocellular cccDNA P region during drug withdrawal, most detectable mutations were L/F/Q/R267H (25/43), V278T (18/43), N/H238T (15/43), D134E/I (14/43), and T222A (11/43). During relapse, the highest detectable mutation rates in serum rcDNA P region were N/H238T (12/19), L/F/Q/R267H (10/19), T222A (10/19), and V278T (8/19).

Conclusion: High mutation rates of T222A and N/H238T in P region of HBV DNA increase the risk of relapse in patients. As a result, patients are susceptible to relapse after drug withdrawal.

Effect of dexmedetomidine on convalescence quality after general anesthesia and postoperative delirium, and on cognitive function in elderly patients undergoing lower limb surgery

Wenbo Wei — 2023-11-06

Purpose: To investigate the effect of different doses of dexmedetomidine on the quality of postoperative recovery, incidence of postoperative delirium, and cognitive function in elderly patients undergoing lower limb surgery.

Methods: A total of 112 patients who received treatment in the Department of Anesthesiology, Affiliated Hospital of Inner Mongolia Medical University, Hothot, China from January 2021 to January 2023 were divided into 3 groups, consisting of low-dose group (35 patients received 0.2 mg/kg), medium-dose group (39 patients received 0.4 mg/kg), and high-dose group (38 patients received 0.6 mg/kg). Parameters including, convalescence quality of general anesthesia, incidence of postoperative delirium, adverse reactions, Mini- mental State Examination (MMSE) scores, sedation effect (Ramsay), analgesia effect (visual analogue scale (VAS)), and stress indices, viz, norepinephrine (NE), epinephrine (E), and cortisol (COR) levels), were evaluated and compared.

Results: There was no significant difference in tracheal extubation time, recovery time of spontaneous breathing, calling eye-opening time, or full awakening time among the three groups (p > 0.05). However, MMSE score was significantly higher in low-dose group on days 1 and 3 after surgery (p < 0.05) and VAS scores were significantly higher in low-dose group at 12 and 24 h after recovery compared to other groups (p < 0.05). Ramsay score was significantly higher in high-dose group (p < 0.05). Levels of NE, E, and COR were significantly lower in medium-dose group compared to other groups (p < 0.05). Incidence of adverse reactions were significantly lower in low and medium-dose groups compared to high- dose group (p < 0.05).

Conclusion: Medium-dose dexmedetomidine demonstrates favorable sedative and analgesic effects with minimal impact on cognitive function and stress response in elderly patients undergoing lower limb surgery. Furthermore, it does not affect quality of postoperative recovery nor incidence of postoperative delirium. More large-scale, randomized controlled studies are needed to confirm these results.

Effect of the combination of oseltamivir, artificial cowbezoar, chlorphenamine maleate, and interferon nebulization on immune function in children with influenza

Xianjie Wu — 2023-11-06

Purpose: To determine the effect of combining oseltamivir, artificial cow-bezoar, chlorphenamine maleate, and interferon inhalation on immune function and serum amyloid A (SAA) levels in children with influenza.

Methods: A total of 114 children with influenza treated at the Second Affiliated Hospital of Hainan Medical University, Hainan Province, China from December 2019 to December 2022 were randomly divided into two groups, viz, study group (n = 57) and control group (n = 57). Control group received oseltamivir sodium chloride infusion, artificial cow-bezoar, and chlorphenamine maleate granules. Study group was treated with interferon alpha-1b in addition to control group treatment. Their clinical symptoms, duration of symptoms, immune function, SAA and C-reactive protein (CRP) levels were determined before and after treatment. Adverse reactions were also recorded.

Results: Study group had a significantly shorter duration of fever, cough, sore throat, and nasal congestion after 5 days of treatment than control group (p < 0.05). The study group also showed higher CD3+ and CD8+ levels and lower CD4+ and CD4+/CD8+ levels than control group after treatment. However, both groups showed lower levels of SAA, CRP, and SAA/CRP after treatment than before treatment (p < 0.05). Furthermore, the levels of SAA, CRP, and SAA/CRP were lower in study group than in control group after treatment (p < 0.05). The incidence of adverse reactions in the study group after treatment was significantly lower than in the control group (p < 0.05).

Conclusion: Quadruple therapy using oseltamivir, artificial cow-bezoar, chlorphenamine maleate, and interferon inhalation significantly shortens symptoms, boost immunity, lower SAA levels, and reduce side effects in children with influenza.

Synergistic effect of continuous care and cephalosporin antimicrobials in managing pulmonary infections in acute stroke patients: A comprehensive study

Lanqing W — 2023-11-06

Purpose: To investigate potential benefits of continuous nursing combined with cephalosporin antibiotics in patients with acute cerebral infarction complicated by pulmonary infection.

Methods: A total of 106 patients diagnosed with acute cerebral infarction complicated by pulmonary infection were selected for this study, and admitted to The Second Affiliated Hospital of Hainan Medical University, Haikou, China from June 2020 to June 2022. Patients were randomly divided into a control group (which received conventional care and cephalosporin antibiotics, n =53), and a study group managed with sustained nursing and cephalosporin antibiotics (n = 53). The study compared various clinical parameters between two groups before and after intervention, including time of symptom relief for fever, cough, and wet rales, as well as the National Institutes of Health Stroke Scale (NIHSS), FuglMeyer Assessment (FMA), Barthel Index (BI), Self-Perceived Burden Scale (SPBS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and severity of pulmonary infection which was assessed by CURB 65 score.

Results: Compared with control group, study group had a significantly shorter clinical symptom relief time after intervention (p < 0.05). After intervention, NIHSS, SPBS, SAS, SDS, APACHE II, and CURB 65 scores in study group were significantly lower, whereas FMA and BI scores were significantly higher before intervention (p < 0.05).

Conclusion: Administration of nursing care and cephalosporin antibiotics reduces the time required for symptom relief, and improves neurological function in patients with acute cerebral infarction and pulmonary infections.

Effect of sodium zirconium cyclosilicate in combination with insulin and glucose infusion on hyperkalemia treatment

Xuansheng Wu — 2023-11-06

Purpose: To evaluate the efficacy of sodium zirconium cyclosilicate (SZC) in combination with insulinand glucose infusion in managing hyperkalemia.

Methods: A total of 126 patients, who were admitted with hyperkalemia (≥ 5 mmol/L) to the Yongchuan District Hospital of Traditional Chinese Medicine, Chongqing, China from January 2021 to December 2022, were retrospectively studied. Participants were divided into three groups based on different potassium-lowering regimens, viz, SZC group (40 patients), insulin with glucose (IG) group (38 patients) and SZC + IG group (48 patients). Changes in potassium levels, other serum electrolytes (magnesium, sodium, phosphate, calcium), alanine aminotransferase (ALT) and albumin before and after treatment were recorded. Adverse reactions during treatment were also recorded.

Results: Post-treatment, the potassium levels in all three groups exhibited a significant reduction when compared to pre- treatment values (p < 0.05). The SZC + IG group showed the highest efficacy, with a significant reduction in blood potassium levels observed 4 h after administration, which was more pronounced compared to other groups. The SZC + IG group, maintained potassium ion concentration at a normal level for a longer duration and no serious adverse reactions were observed during treatment.

Conclusion: Intervention with SZC + IG lowers blood potassium levels, maintains it within normal range, and is more effective than the individual use of SZC or IG. A combination of sodium zirconium cyclosilicate, insulin and glucose infusion for treating hyperkalemia will need to be investigated further in a large-scale multicenter study.

Effectiveness of the combination of terbutaline and budesonide inhalation in treating acute bronchial asthma during pregnancy

Guozhi Zhang — 2023-11-06

Purpose: To investigate the therapeutic benefits of terbutaline sulfate aerosol inhalation combined with budesonide, and its influence on pulmonary function in pregnant women suffering from acute bronchial asthma attacks.

Methods: A total of 100 pregnant patients diagnosed with acute bronchial asthma in PLA Strategic Support Force Characteristic Medical Center, Beijing, China were divided into control and study groups (n = 50 each). Control group received aerosol inhalation of normal saline along with standard treatments, viz, oxygen inhalation, sputum aspiration, anti-infection measures, and maintenance of water- electrolyte balance. Study group received combined terbutaline sulfate and budesonide aerosol inhalation in addition to standard treatment. Both groups underwent a 7-day treatment course, with inhalation therapy twice daily.

Results: Study group showed significantly shorter relief times for cough, wheezing, and chest tightness compared to control group (p < 0.05). After treatment, 92.0 % of patients in study group exhibited improvement or relief from their symptoms, compared to 80.0 % in control group (p < 0.05). Pulmonary function indices, including first vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and FEV1/FVC, improved in both groups after treatment. Study group exhibited significantly lower laboratory indices, including immunoglobulin E (IgE), C-reactive protein (CRP), and eosinophils (EOS) compared to control group (p < 0.05).

Conclusion: The combination of inhalation therapy of terbutaline sulfate with budesonide in pregnant women experiencing acute bronchial asthma demonstrates significant enhancements in clinical effectiveness, pulmonary function, and laboratory parameters. Clinical trials of this combined therapy should be carried out in other locations to ascertain the effect of population variation on treatment efficacy.

Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

Aihong Yang — 2023-11-06

Nectin-3 and nectin-4 belong to the immunoglobulin (Ig) superfamily, and are Ca²⁺ -independent homophilic cell adhesion molecules. Nectin-3 is ubiquitous in adult tissues, and it enhances normal levels of synaptic formation. In contrast, nectin-4 is weakly-to-moderately expressed in normal human tissues. In recent years, studies have shown that nectin-3 is highly expressed in the nervous system. Moreover, it is associated with poor prognostic factors in distant metastases and malignant tumors with high vascular invasion such as pancreatic, lung and breast cancers. In particular, nectin-4 is overexpressed in various malignant tumors, and it is associated with proliferation, angiogenesis, metastasis, drug resistance, tumor relapse, DNA repair, cancer stemness, and poor prognosis. Unlike nectin-3, nectin-4 has become a potential prognostic biomarker and specific therapeutic target for cancer as there is no consensus on the significance of abnormal expression of nectin-3 in various cancers.