Effectiveness and safety of the ablative fractional 2940-nm Er: YAG laser for the treatment of androgenetic alopecia.

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.

A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. METHODS: We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. RESULTS: We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. CONCLUSIONS: Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.

Identification of NPF Family Genes in Brassica rapa Reveal Their Potential Functions in Pollen Development and Response to Low Nitrate Stress.

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.

[Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology].

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

ADAR1 Stimulation by IFN-α Downregulates the Expression of MAVS via RNA Editing to Regulate the Anti-HBV Response.

The partial response of chronic hepatitis B virus (CHB) patients to interferon-α (IFN-α) therapy remains elusive, which requires a better understanding of the involved molecular mechanism. In our study, bioinformatics analysis was applied to relate IFN-α regulated candidate genes and RNA editing sites by RNA sequencing. Mitochondrial antiviral signaling protein (MAVS) antiviral effect was confirmed in HepG2.2.15 cells and in two mouse models. The associations between polymorphisms in MAVS gene and response to IFN-α therapy were confirmed in CHB patients. We found that IFN-α downregulates MAVS via RNA editing that was mediated by adenosine deaminase acting on RNA (ADAR1). ADAR1 inhibited MAVS expression via a human antigen R (HuR)-mediated post-transcriptional regulation. MAVS exerted an antiviral activity and reduced the level of hepatitis B virus (HBV) markers in vitro and in vivo. IFN-α antiviral effects were significantly enhanced by MAVS co-transfection. Hepatitis B core protein (HBc) interacted with SP1 to inhibit the promoter activity of MAVS that regulates its expression. CHB patients with a rs3746662A allele had higher MAVS expression and thus were more responsive to IFN-α treatment. In this work, we demonstrated that the decrease of MAVS expression is mediated by the IFN-α-ADAR1 axis. This study also highlighted the potential for the clinical application of MAVS in combination with IFN-α for the treatment of HBV infection.

Kartogenin regulates hair growth and hair cycling transition.

Background: Kartogenin is a heterocyclic compound able to promote the proliferation, migration, and differentiation of various cell types and induce cartilage-like tissue regeneration. However, the role of kartogenin in hair follicles (HFs), remains unknown. We therefore investigated the effects of kartogenin on the regulation of hair growth and hair growth cycle transition. Methods: The effects of kartogenin on the proliferation, cell cycle status, and migration of primary human outer root sheath cells (ORSCs) were evaluated by MTS assay, flow cytometry, Transwell® and scratch assays, respectively. We exposed ORSCs to kartogenin (1 µM) and determined changes in mRNA and protein levels of transforming growth factor (TGF)-ß2/Smad signaling molecules by reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. We also examined the effects of kartogenin (10 µM) on HFs in mice by histology following cutaneous injection. Results: Kartogenin enhanced ORSC proliferation and migration function in a dose-dependent manner, and downregulated the expression of TGF-ß2/Smad signaling molecules in vitro. Injection of kartogenin delayed catagen phase and increased regenerated hair length in mice in vivo. Conclusions: Kartogenin modulates HF growth and regulates the hair cycle and the TGF-ß2/Smad signaling pathway, providing a potential new approach for the treatment of hair loss.

Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.

PURPOSE: Castration-resistant prostate cancer (CRPC) is the most common cause of death in men. The effectiveness of HDAC inhibitors has been demonstrated by preclinical models, but not in clinical studies, probably due to the ineffectively accumulation of HDACI in prostate cancer cells. The purpose of this work was to evaluate effects of a novel HDACI (CN133) on CRPC xenograft model and 22Rv1 cells, and develops methods, PET/CT imaging, to detect the therapeutic effects of CN133 on this cancer. METHODS: We designed and performed study to compare the effects of CN133 with SAHA on the 22Rv1 xenograft model and 22Rv1 cells. Using PET/CT imaging with [11C] Martinostat and [18F] FDG, we imaged mice bearing 22Rv1 xenografts before and after 21-day treatment with placebo and CN133 (1 mg/kg), and uptake on pre-treatment and post-treatment imaging was measured. The anti-tumor mechanisms of CN133 were investigated by qPCR, western blot, and ChIP-qPCR. RESULTS: Our data showed that the CN133 treatment led to a 50% reduction of tumor volume compared to the placebo that was more efficacious than SAHA treatment in this preclinical model. [11C] Martinostat PET imaging could identify early lesions of prostate cancer and can also be used to monitor the therapeutic effect of CN133 in CRPC. Using pharmacological approaches, we demonstrated that effects of CN133 showed almost 100-fold efficacy than SAHA treatment in the experiment of cell proliferation, invasion, and migration. The anti-tumor mechanisms of CN133 were due to the inhibition of AR signaling pathway activity by decreased HDAC 2 and 3 protein expressions. CONCLUSION: Taken together, these studies provide not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. These results will likely lead to human trials in the future.

Comparing the characteristics and predicting the survival of patients with head and neck melanoma versus body melanoma: a population-based study.

BACKGROUND: Previous studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM. METHODS: The information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots. RESULTS: Of 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785-0.896) and AUC values (0.81-0.925), and the calibration plots showed great consistency. CONCLUSIONS: The characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.

Expression and localization of Sox10 during hair follicle morphogenesis and induced hair cycle.

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.

The transcription factor FgMed1 is involved in early conidiogenesis and DON biosynthesis in the plant pathogenic fungus Fusarium graminearum.

Fusarium graminearum is a prominent fungal pathogen that causes economically important losses by infesting a wide variety of cereal crops. F. graminearum produces both asexual and sexual spores which disseminate and inoculate hosts. Therefore, to better understand the disease cycle and to develop strategies to improve disease management, it is important to further clarify molecular mechanisms of F. graminearum conidiogenesis. In this study, we functionally characterized the FgMed1, a gene encoding an ortholog of a conserved MedA transcription factor known to be a key conidiogenesis regulator in Aspergillus nidulans. The gene deletion mutants ΔFgMed1 produced significantly less conidia, and these were generated from abnormal conidiophores devoid of phialides. Additionally, we observed defective sexual development along with reduced virulence and deoxynivalenol (DON) production in ΔFgMed1. The GFP-tagged FgMed1 protein localized to the nuclei of conidiophores and phialides during early conidiogenesis. Significantly, RNA-Seq analyses showed that a number of the conidiation- and toxin-related genes are differentially expressed in the ΔFgMed1 mutant in early conidiogenesis. These data strongly suggest that FgMed1 involved in regulation of genes associated with early conidiogenesis, DON production, and virulence in F. graminearum.

Anode modification with capacitive materials for a microbial fuel cell: an increase in transient power or stationary power.

Extensive efforts have been devoted to improve the anode performance of a microbial fuel cell (MFC) by using modified carbon-based anode materials, but most of them did not recognize that the power performance measured by the commonly-used varying circuit resistance (VCR) or linear sweep voltammetry (LSV) method was overestimated due to the effect of anode capacitance. Here, we examined and compared the transient power and the stationary power of a series of MFCs equipped with the polypyrrole-graphene oxide (PPy-GO)-modified graphite felt anodes. It was found that noticeable transient power was recorded when the VCR or LSV method was chosen for power measurements. Calculations on the contribution of different sources to the measured maximum power density showed that the discharge of bio-electrons stored in the high-capacitance anode was a dominant contributor, especially when the time duration (for the VCR method) was not sufficiently long or the scan rate (for the LSV method) was not sufficiently low. Although anode modification with capacitive materials can result in the increased stationary power obtained from the fed-batch cycle test, owing to the increases in the anode surface area and the number of bacteria attached to anode, the increase in the transient power was more remarkable.

Concentrated growth factor therapy as cosmetic treatment in discoid lupus erythematosus.

Discoid lupus erythematosus (DLE) is a disfigurement disease. The atrophic scar and hair loss of this disease are followed by cosmetic defects and profoundly impact psychological health. Concentrated growth factor (CGF) has been widely adopted in medical cosmetology. Here we report a 36-year-old female systemic lupus erythematosus patient with a 5-year history of alopecia in DLE, who was recommended for CGF therapy and experienced hair regrowth. We suggest that CGF may be an effective cosmetic treatment for DLE.

Fermented dietary fiber from soy sauce residue exerts antidiabetic effects through regulating the PI3K/AKT signaling pathway and gut microbiota-SCFAs-GPRs axis in type 2 diabetic mellitus mice.

The gut plays a crucial role in the development and progression of metabolic disorders, particularly in relation to type 2 diabetes mellitus (T2DM). While a high intake of dietary fiber is inversely associated with the risk of T2DM, the specific effects of various dietary fibers on T2DM are not fully understood. This study investigated the anti-diabetic properties of fermented dietary fiber (FDF) derived from soy sauce residue in T2DM mice, demonstrating its ability to lower blood glucose levels and ameliorate insulin resistance. Our findings revealed that FDF could enhance hepatic glucose metabolism via the IRS-1/PI3K/AKT/mTOR pathway. Additionally, the anti-diabetic effect of FDF was correlated with alterations in gut microbiota composition in T2DM mice, promoting a healthier gut environment. Specifically, FDF increased the abundance of beneficial flora such as Dubosiella, Butyricimonas, Lachnospiraceae_NK4A136_group, Lactobacillus and Osillibacter, while reducing harmful bacteria including Bilophila, Parabacteroides and Enterorhabdus. Further analysis of microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs), provided evidence of FDF's regulatory effects on cecal contents in T2DM mice. Importantly, FDF treatment significantly restored the G-protein-coupled receptors (GPRs) expression in the colon of T2DM mice. In conclusion, our study suggests that the anti-diabetic effects of FDF are associated with the regulation of both the liver-gut axis and the gut microbiota-SCFAs-GPRs axis.

Dietary nobiletin regulated cefuroxime- and levofloxacin-associated "gut microbiota-metabolism" imbalance and intestinal barrier dysfunction in mice.

Nobiletin (NOB) exhibits significant biological activities and may be a potential dietary treatment for antibiotic-associated gut dysbiosis. In this study, mice were gavaged with 0.2 mL day-1 of 12.5 g L-1 cefuroxime (LFX) and 10 g L-1 levofloxacin (LVX) for a duration of 10 days, accompanied by 0.05% NOB to investigate the regulatory effect and potential mechanisms of NOB on antibiotic-induced intestinal microbiota disorder and intestinal barrier dysfunction. Our results indicated that dietary NOB improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins (TJs) and the number of goblet cells. Furthermore, dietary NOB reduced the levels of serum lipopolysaccharide (LPS) and pro-inflammatory factors (TNF-α and IL-1ß), thereby facilitating the restoration of the intestinal mucosal barrier. Additionally, dietary NOB increased the abundance of beneficial bacteria f_Lachnospiraceae and regulated the metabolic disorders of short-chain fatty acids (SCFAs) and bile acids (BAs). Notably, NOB supplementation resulted in elevated levels of butyric acid and lithocholic acid (LCA), which contributed to the repair of the intestinal mucosal barrier function and the maintenance of intestinal homeostasis. Collectively, our results propose a healthy dietary strategy for the prevention or mitigation of antibiotic-associated gut dysbiosis by dietary NOB.

Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.

Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.

Correction: Synthesis of vertically aligned carbon nanotube arrays on polyhedral Fe/Al2O3 catalysts.

Correction for 'Synthesis of vertically aligned carbon nanotube arrays on polyhedral Fe/Al2O3 catalysts' by Jun Liu et al., Chem. Commun., 2011, 47, 6434-6436, https://doi.org/10.1039/C1CC10878F.

PPM1H is down-regulated by ATF6 and dephosphorylates p-RPS6KB1 to inhibit progression of hepatocellular carcinoma.

We have shown previously that polymorphism of activating transcription factor 6 (ATF6) is associated with susceptibility to hepatocellular carcinoma (HCC). Therefore, genes down-regulated by ATF6 might play a tumor-suppressing role. In the present study, we identified that expression of protein phosphatase magnesium- or manganous-dependent 1H (PPM1H) mRNA and protein can be inhibited by ATF6 in hepatoma cells and mice with liver Atf6 knockdown. Tumor tissues from 134 HCC patients were analyzed by immunohistochemistry, and PPM1H exhibited higher expression levels in adjacent para-cancer tissues than in HCC tissues. Therefore, patients with higher expression of PPM1H had a better prognosis. PPM1H inhibited proliferation, migration, and invasion of hepatoma cells. In addition, PPM1H inhibited induced HCC nodule formation as well as tumor xenograft growth in diethylnitrosamine/CCl4-induced HCC mouse model and nude mouse tumorigenicity assay, respectively. A 3D model of PPM1H was obtained by homology multi-template modeling, and ribosomal protein S6 kinase B1 (RPS6KB1) in the bone morphogenetic protein (BMP)/transforming growth factor ß (TGF-ß) pathway was screened out as the potential substrate of PPM1H by Rosetta. PPM1H could directly dephosphorylate p-RPS6KB1. To conclude, we discovered RPS6KB1 as a new PPM1H dephosphorylation substrate. PPM1H exhibited a suppressive effect on HCC progression by dephosphorylating p-RPS6KB1.

Dietary 5-demethylnobiletin prevents antibiotic-associated dysbiosis of gut microbiota and damage to the colonic barrier.

5-Demethylnobiletin (5DN) is an important ingredient of citrus extract that is rich in polymethoxyflavones (PMFs). In this study, we systemically investigated the preventive effects of 5DN on antibiotic-associated intestinal disturbances. Experimental mice were gavaged 0.2 mL per day of the antibiotic cocktail (12.5 g L-1 cefuroxime and 10 g L-1 levofloxacin) for 10 days, accompanied by dietary 0.05% 5DN for 10 and 20 days. The results showed that the combination of cefuroxime and levofloxacin caused swelling of the cecum and injury to the colon tissue. Meanwhile, the balance of intestinal oxidative stress and the barrier function of mice was also damaged by the antibiotics through upregulation of the relative mRNA levels of superoxide dismutase 3 (SOD3), quinine oxidoreductase 1 (NQO1) and glutathione peroxidase 1 (GPX1), and downregulation of the relative protein levels of tight junction proteins (TJs). Moreover, antibiotic exposure led to disorder of the gut microbiota, particularly increased harmful bacteria (Proteobacteria) and decreased beneficial bacteria (Bacteroideta). However, dietary 5DN could reduce antibiotic-associated intestinal damage, evidenced by the results that 5DN alleviated gut oxidative damage and attenuated intestinal barrier injury via increasing the expression of TJs including occludin and zonula occluden1 (ZO1). Additionally, dietary 5DN modulated the composition of the gut microbiota in antibiotic-treated mice by increasing the relative levels of beneficial bacteria, such as Dubosiella and Lactobacillus. Moreover, PMFs increased the contents of isobutyric acid and butyric acid, which were almost eliminated by antibiotic exposure. In conclusion, 5DN could alleviate antibiotic-related imbalance of intestinal oxidative stress, barrier function damage, intestinal flora disorders and the reduction of short-chain fatty acids (SCFAs), which lays a foundation for exploring safer and more effective ways to prevent or mitigate antibiotic-associated intestinal damage.

The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients.

Background: JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking. Objective: Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis. Methods: Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata. Results: 6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions. Limitations: Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data. Conclusion: JAK inhibitors are effective in alopecia areata, although associated with an increased risk.