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.

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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle.

Alopecia is a common progressive disorder associated with abnormalities of the hair follicle cycle. Hair follicles undergo cyclic phases of hair growth (anagen), regression (catagen), and rest (telogen), which are precisely regulated by various mechanisms. However, the specific mechanism associated with hair follicle cycling, which includes noncoding RNAs and regulation of competitive endogenous RNA (ceRNA) network, is still unclear. We obtained data from publicly available databases and performed real-time quantitative polymerase chain reaction validations. These analyses revealed an increase in the expression of miRNAs and a decrease in the expression of target mRNAs and lncRNAs from the anagen to telogen phase of the murine hair follicle cycle. Subsequently, we constructed the ceRNA networks and investigated their functions using enrichment analysis. Furthermore, the androgenetic alopecia (AGA) microarray data analysis revealed that several novel alopecia-related genes were identified in the ceRNA networks. Lastly, GSPT1 expression was detected using immunohistochemistry. Our analysis revealed 11 miRNAs (miR-148a-3p, miR-146a-5p, miR-200a-3p, miR-30e-5p, miR-30a-5p, miR-27a-3p, miR-143-3p, miR-27b-3p, miR-126a-3p, miR-378a-3p, and miR-22-3p), 9 target mRNAs (Atp6v1a, Cdkn1a, Gadd45a, Gspt1, Mafb, Mitf, Notch1, Plk2, and Slc7a5), and 2 target lncRNAs (Neat1 and Tug1) were differentially expressed in hair follicle cycling. The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth-related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.

Association analysis of rice resistance genes and blast fungal avirulence genes for effective breeding resistance cultivars.

Utilization of rice blast-resistance (R) genes is the most economical and environmentally friendly method to control blast disease. However, rice varieties with R genes influence the outcome of genetic architectures of Magnaporthe oryzae (M. oryzae), and mutations in avirulence (AVR) genes of M. oryzae may cause dysfunction of the corresponding R genes in rice varieties. Although monitoring and characterizing rice R genes and pathogen AVR genes in field populations may facilitate the implementation of effective R genes, little is known about the changes of R genes over time and their ultimate impact on pathogen AVR genes. In this study, 117 main cultivated rice varieties over the past five decades and 35 M. oryzae isolates collected from those diseased plants were analyzed by PCR using gene-specific markers of the nine R genes and six primer pairs targeting the coding sequence or promoter of AVR genes, respectively. The R genes Pigm, Pi9, Pi2, Piz-t, Pi-ta, Pik, Pi1, Pikp, and Pikm were identified in 5, 0, 1, 4, 18, 0, 2, 1, and 0 cultivars, respectively. Significantly, none of these R genes had significant changes that correlated to their application periods of time. Among the four identified AVR genes, AVR-Pik had the highest amplification frequency (97.14%) followed by AVR-Pita (51.43%) and AVR-Pi9 (48.57%); AVR-Piz-t had the lowest frequency (28.57%). All these AVR genes except AVR-Pi9 had 1-2 variants. Inoculation mono-genic lines contained functional genes of Pi2/9 and Pik loci with 14 representative isolates from those 35 ones revealed that the presence of certain AVR-Piz-t, AVR-Pita variants, and AVR-Pik-E + AVR-Pik-D in M. oryzae populations, and these variants negated the ability of the corresponding R genes to confer resistance. Importantly, Pi2, Pi9, and Pigm conferred broad-spectrum resistance to these local isolates. These findings reveal that the complex genetic basis of M. oryzae and some effective blast R genes should be considered in future rice blast-resistance breeding programs.

Frontal fibrosing alopecia: A review of disease pathogenesis.

Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia that mostly affects postmenopausal women and causes frontotemporal hairline regression and eyebrow loss. Although the incidence of FFA has increased worldwide over the last decade, its etiology and pathology are still unclear. We cover the latest findings on its pathophysiology, including immunomodulation, neurogenic inflammation, and genetic regulation, to provide more alternatives for current clinical treatment. A persistent inflammatory response and immune privilege (IP) collapse develop and lead to epithelial hair follicle stem cells (eHFSCs) destruction and epithelial-mesenchymal transition (EMT) in the bulge area, which is the key process in FFA pathogenesis. Eventually, fibrous tissue replaces normal epithelial tissue and fills the entire hair follicle (HF). In addition, some familial reports and genome-wide association studies suggest a genetic susceptibility or epigenetic mechanism for the onset of FFA. The incidence of FFA increases sharply in postmenopausal women, and many FFA patients also suffer from female pattern hair loss in clinical observation, which suggests a potential association between FFA and steroid hormones. Sun exposure and topical allergens may also be triggers of FFA, but this conjecture has not been proven. More evidence and cohort studies are needed to help us understand the pathogenesis of this disease.

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.

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.