Effects of resveratrol on macrophages after phagocytosis of Candida glabrata.

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.

Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation.

Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models.

Changes in axial length after orthokeratology lens treatment for myopia: a meta-analysis.

PURPOSE: Orthokeratology (OK) lens is a popular optical method to control myopia progression. This study aimed to assess the effect of OK lens on axial length change compared with glasses. METHODS: PubMed, Web of Science, and Embase were searched to retrieve the related articles. Then, the articles were selected according to predefined criteria. Standardized mean difference (SMD) and 95% confidence interval (CI) were selected as effect size for combining and analyzing the change in axial length. RESULTS: A total of 13 articles were included in the present study. Different models were selected according to the heterogeneity of each analysis. The axial length change in OKs group was significantly smaller than control group; SMD (95% CI) of change in axial length was - 0.857 (- 1.146, - 0.568), p < 0.001 at the end of 1 year and - 0.701 (- 1.675, 0.272), p < 0.001 at the end of 2 years or longer time. CONCLUSIONS: OK lens treatment appears more effective in slowing axial elongation than glasses during the early treatment of myopia in children.

Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel.

Despite improvements in the prognosis of osteosarcoma patients, chemotherapy fails in a considerable number of cases due to drug resistance. The development of novel agents may enhance chemosensitivity. This study explored the anticancer function of polydatin and its ability-in combination with paclitaxel-to overcome drug resistance in human osteosarcoma U-2OS and MG-63 cell lines. A cell proliferation assay (celll counting kit-8), a cell-cycle assay, an apoptosis assay (annexin V-fluorescein isothiocyanate/propidium iodide), and a cell migration assay (Transwell) were used to analyze cell activity. Western blot analysis and quantitative reverse-transcription polymerase chain reaction were performed to examine function-related mRNA and protein levels. Treatment with polydatin suppressed cell growth and migration in both cell lines. Moreover, polydatin induced cell apoptosis in both parental and paclitaxel-resistant cells, and cell-cycle arrest in the S phase. Furthermore, it altered the expression of various proteins associated with cell growth (Ki67, p21, cyclin A, cyclin E, and cyclin-dependent kinase 2), migration (matrix metalloproteinase-2 [MMP-2], MMP-9, and tissue inhibitor of metalloproteinase-1), apoptosis (poly[ADP-ribose] polymerase 1 and caspase 3), and drug resistance (p-glycoprotein 1, lung resistance-related protein 1, growth arrest and DNA damage-45α, glutathione S-transferase π, and heat shock protein 27) in paclitaxel-resistant osteosarcoma cells. Cells transfected with myr-Akt caused obvious upregulation and activation of Akt, which were significantly attenuated via polydatin treatment. In conclusion, polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel.

The safety and efficacy of daylight photodynamic therapy in the treatment of actinic keratoses: a systematic review and meta-analysis.

Daylight photodynamic therapy (DLPDT) is a novel therapeutic approach for actinic keratoses (AKs). This study aimed to evaluate the safety and efficacy of DLPDT in treating patients with AKs as compared to conventional photodynamic therapy (CPDT). PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for relevant randomized controlled trials (RCTs) published before November 2017, based on the following search terms: "solar keratoses", "actinic keratoses", "photodynamic therapy", "daylight photodynamic therapy", "conventional photodynamic therapy", and "randomized". The complete response rate, patient satisfaction, and patient-reported pain after intervention with DLPDT or CPDT were primarily measured. Sensitivity analysis was conducted to determine the reliability of results. Begg's and Egger's tests were used to assess the likelihood of publication bias. Eight RCTs, comprising a total of 424 patients with AKs treated with DLPDT or CPDT, were included. No significant difference was found between the lesion response rate and the mean lesion response in a comparison of DLPDT and CPDT treatments. Generally, DLPDT was associated with higher patient satisfaction than CPDT. The patients who underwent DLPDT experienced less pain than those who underwent CPDT. Most of our results were of high stability and low sensitivity. Meanwhile, no statistical evidence of publication bias among studies was found under all comparisons. In conclusion, DLPDT is a safe and effective therapy, which could help in selecting the most appropriate therapeutic method for treating AKs and in guiding physicians to optimize treatment strategies.

Graft survival rate of deep anterior lamellar keratoplasty for keratoconus: A meta-analysis.

BACKGROUND: Deep anterior lamellar keratoplasty (DALK) is an optional treatment for patients with keratoconus, and the associated graft survival rate varies. Herein, we aimed to explore the graft survival rate of DALK in patients with keratoconus. METHODS: PubMed, Web of Science, and ProQuest databases were searched to retrieve the related articles. General data, clinical characters, and graft survival rates were obtained directly from the included studies and analyzed by meta-analysis. RESULTS: A total of 12 articles were included. The merged 1-, 3-, and 5-year graft survival rates were 100% (99.9-100%, P < .001), 92.9% (89.8-95.9%, P < .001), and 90.4% (86.0-0.948%, P < .001), respectively. Lower heterogeneity was shown in each subgroup that was divided neither according to the sample number nor number of surgeons. CONCLUSION: The survival rate slightly decreases year by year, but the overall trend seems relatively stable. Ensuring that all DALK procedures are performed by a single surgeon might be helpful to improve the graft survival rate after surgery.

NGF and PI3K/Akt signaling participate in the ventral motor neuronal protection of curcumin in sciatic nerve injury rat models.

OBJECTIVE: It has been reported that sciatic nerve injury (SNI) leads to degeneration, damage, and apoptosis of motor neurons. Nerve growth factor (NGF) plays a pivotal role in regeneration and reestablishment of neuronal function via activating PI3K/Akt survival signaling pathways. Curcumin owns neuroprotective effect following brain injury. In the present study, we attempt to investigate underlying mechanism of neuroprotective effect of curcumin through elucidating its correlation with NGF and PI3K/Akt signaling pathways in vitro and in vivo. METHODS: PC-12 cells were exposed H2O2 in order to induce neuron cell injury and cells were then treated with curcumin. Caspase-3, NGF level and Akt phosphorylation were determined using flow cytometry and western blotting. Then, cells were treated with NGF specific siRNA followed by measurement of apoptosis, NGF and Akt phosphorylation levels. In animal model, rats were subjected to SNI and then randomly designated into four different groups: curcumin, curcumin + LY294002, curcumin + NGF shRNA, and negative controls and 12 rats in each group (n = 12). After four weeks of continuous treatment, tissue samples were obtained and subjected to TUNEL, NeuN double staining and western blotting. RESULTS: Curcumin significantly reduced the number of apoptotic cells induced by H2O2 and this effect was associated with upregulation of TrkA, Akt and downregulation of p17. ProNGF level was significantly decreased while mature NGF level was increased with curcumin treatment. When NGF was suppressed, anti-apoptotic effect of curcumin was attenuated. In addition, inhibition of PI3K/Akt results in increased apoptotic rate compared to vehicles following curcumin treatment which was reflected by decreased p17, Ki67, and cyclin D1. Suppression of NGF and inhibition of PI3K led to increased neuron cell death through increasing proNGF and decreasing mNGF, Akt, TrkA, p75NTR, and p17. CONCLUSION: Our findings revealed that curcumin exerts its protective effect against injured neurons through stimulating NGF release which further activates TrkA and PI3K/Akt cell survival signaling.