Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.

BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options. METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables. RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression. CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.

NAT10-mediated ac4C modification promotes stemness and chemoresistance of colon cancer by stabilizing NANOGP8.

Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

Mechanism of Action of "Astragali Radix-Cassia Twig-Poria" in Chronic Heart Failure: A Network Pharmacology Approach.

This study utilizes network pharmacology analysis to investigate the components, targets, and pathways involved in the treatment of chronic heart failure (CHF) with the combination of "Astragali Radix-Cassia Twig-Poria." The TCMSP, GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases were utilized to identify the active ingredients and targets of this combination for CHF. Protein interactions were derived from the STRING database, and Cytoscape was used to construct the "drug-component-target-disease" network and protein interactions network. The GO function and KEGG signaling pathway were enriched, and molecular docking was performed to verify the stability of the core components and their targets. The study identified 41 active ingredients, 101 targets (including 94 related to CHF), 9 core targets, and 26 core ingredients of "Astragali Radix-Cassia Twig-Poria." Additionally, 1444 GO entries and 140 KEGG pathways (including 36 related to CHF) were found. Molecular docking results confirmed the binding ability of the combination to core targets. Overall, this study provides valuable insights into the key components, targets, and pathways involved in the treatment of CHF with "Astragali Radix-Cassia Twig-Poria," contributing to further research on its pharmacological effects.

Facial Physiological Characteristics and Skin Microbiomes Changes are Associated with Body Mass Index (BMI).

Background: Overweight and obesity have become public health problems worldwide. An increasing number of research works are focusing on skin physiology and the manifestations of obesity-associated skin diseases, but little is known about the correlations between body mass index (BMI), facial skin physiological parameters, and the facial skin microbiome in healthy women. Objective: To investigate the correlations between BMI, facial skin physiological parameters and facial bacteria and fungi in 198 women aged 18 to 35 years in Shanghai. Methods: According to the international BMI standard and Chinese reference standard, subjects were divided into three groups, "lean" B1, "normal" B2 and "overweight" B3, and the physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiota was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: Compared with the skin physiological parameters of the normal group, those of the overweight group exhibited a significant increase in trans-epidermal water loss (TEWL), which indicated that the skin barrier was impaired. The skin haemoglobin content was significantly increased, and skin surface pH was significant decreased in those with a high BMI. Furthermore, α-diversity, analysed using the Shannon, Chao, Sobs, and Ace indexes, was increased in the overweight group, suggesting that the diversity and species abundance of facial bacterial and fungal microbiota were also increased. Moreover, the overweight group had higher abundances of Streptococcus, Corynebacterium, Malassezia, and Candida. Notably, skin surface pH was significantly and negatively correlated with the relative abundances of Malassezia, Candida, and Cladosporium. Besides, the abundance of Malassezia was positively associated with the abundances of Staphylococcus and Corynebacterium. Conclusion: These results indicate that BMI is associated with differences in the biophysical properties and microbiome of the facial skin. A high BMI affects the integrity of skin barrier and changes the skin flora diversity and species composition.

Protective effect of Bifidobacterium animalis CGMCC25262 on HaCaT keratinocytes.

Bifidobacteria are the most prevalent members of the intestinal microbiota in mammals and other animals, and they play a significant role in promoting gut health through their probiotic effects. Recently, the potential applications of Bifidobacteria have been extended to skin health. However, the beneficial mechanism of Bifidobacteria on the skin barrier remains unclear. In this study, keratinocyte HaCaT cells were used as models to evaluate the protective effects of the cell-free supernatant (CFS), heat-inactivated bacteria, and bacterial lysate of Bifidobacterium animalis CGMCC25262 on the skin barrier and inflammatory cytokines. The results showed that all the tested samples were able to upregulate the transcription levels of biomarker genes associated with the skin barrier, such as hyaluronic acid synthetase (HAS) and aquaporins (AQPs). Notably, the transcription of the hyaluronic acid synthetase gene-2 (HAS-2) is upregulated by 3~4 times, and AQP3 increased by 2.5 times when the keratinocyte HaCaT cells were co-incubated with 0.8 to 1% CFS. In particular, the expression level of Filaggrin (FLG) in HaCaT cells increased by 1.7 to 2.7 times when incubated with Bifidobacterial samples, reaching its peak at a concentration of 0.8% CFS. Moreover, B. animalis CGMCC25262 also decreased the expression of the proinflammatory cytokine RANTES to one-tenth compared to the levels observed in HaCaT cells induced with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). These results demonstrate the potential of B. animalis CGMCC25262 in protecting the skin barrier and reducing inflammatory response.

Complete genome sequence of Cutibacterium acnes type II CCSM0331, isolated from a healthy woman's skin.

The complete genome sequence of Cutibacterium acnes Type II strain CCSM0331, which was isolated from the healthy facial skin, is reported. The assembled 2.5-Mbp genome comprised a single circular chromosome. These data will provide valuable information on the beneficial role of C. acnes as a skin commensal bacteria.

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3XΔMφ), hepatocyte-specific DDX3X knockout (DDX3XΔhep), and wild-type control (DDX3Xfl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3Xfl/fl littermates, DDX3XΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3XΔhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3Xfl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Aqueous extract of Cordyceps cicadae (Miq.) promotes hyaluronan synthesis in human skin fibroblasts: A potential moisturizing and anti-aging ingredient.

Cordyceps cicadae (Miq.) is an edible fungus with unique and valuable medicinal properties that is commonly used in traditional Chinese medicine, but its anti-aging effects on the skin fibroblast are not well studied. The aim of the present study was to analyze the active components of aqueous C. cicadae extract (CCE), determine the effects of CCE on hyaluronan synthesis in human skin fibroblasts, and explore the underlying mechanisms. The results of this study indicate that CCE was rich in polysaccharides, five alditols (mainly mannitol), eight nucleosides, protein, and polyphenols, which were present at concentrations of 62.7, 110, 8.26, 35.7, and 3.8 mg/g, respectively. The concentration of extract required to inhibit 50% of 2,2-azino-bis (3-ethylbenzothiazo-line-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging capacities were 0.36 ± 0.03 and 4.54 ± 0.10 mg/mL, respectively, indicating that CCE exhibits excellent antioxidant activities. CCE showed no cytotoxicity to skin fibroblasts at concentrations ≤ 100 µg/mL, and promoted HA synthesis in fibroblasts. Treatment of fibroblast cells with 100 µg/mL CCE enhances the HA content to 1293 ± 142 ng/mL, which is significantly more than that in the non-treatment (NT) group (p = 0.0067). Further, RNA sequencing detected 1,192 differentially expressed genes (DEGs) in CCE-treated fibroblasts, among which 417 were upregulated and 775 were downregulated. Kyoto Encyclopedia of Genes (KEGG) and Genomes pathway (GO) analysis based on RNA sequencing revealed that CCE mainly affected cytokine-cytokine receptor interaction regulated by HA synthesis-related genes. CCE upregulated HA synthase 2 (HAS2), epidermal growth factor (EGF)-related genes, heparin-binding EGF-like growth factor, C-C motif chemokine ligand 2, interleukin 1 receptor-associated kinase 2, and other genes related to fibroblast differentiation and proliferation. CCE downregulated the gene of matrix metallopeptidase 12 (MMP12), which leads to cell matrix loss. RT-qPCR further verified CCE significantly upregulated HAS2 expression and significantly downregulated MMP12 expression, thus promoting hyaluronan synthesis. CCE shows potential as a moisturizer and anti-aging agent in functional foods and cosmetics.

Hepatocyte DDX3X protects against drug-induced acute liver injury via controlling stress granule formation and oxidative stress.

Drug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF). Continuous and prolonged hepatic cellular oxidative stress and liver inflammatory stimuli are key signatures of DILI. DEAD-box helicase 3, X-linked (DDX3X) is a central regulator in pro-survival stress granule (SG) assembly in response to stress signals. However, the role of DDX3X in DILI remains unknown. Herein, we characterized the hepatocyte-specific role of DDX3X in DILI. Human liver tissues of DILI patients and control subjects were used to evaluate DDX3X expression. APAP, CCl4 and TAA models of DILI were established and compared between hepatocyte-specific DDX3X knockout (DDX3XΔhep) and wild-type control (DDX3Xfl/fl) mice. Hepatic expression of DDX3X was significantly decreased in the pathogenesis of DILI compared with controls in human and mice. Compared to DDX3Xfl/fl mice, DDX3XΔhep mice developed significant liver injury in multiple DILI models. DDX3X deficiency aggravates APAP induced oxidative stress and hepatocyte death by affecting the pro-survival stress granule (SG) assembly. Moreover, DDX3X deficiency induces inflammatory responses and causes pronounced macrophage infiltration. The use of targeted DDX3X drug maybe promising for the treatment of DILI in human.

TATA-box-binding protein promotes hepatocellular carcinoma metastasis through epithelial-mesenchymal transition.

BACKGROUND: HCC characterizes malignant metastasis with high incidence and recurrence. Thus, it is pivotal to discover the mechanisms of HCC metastasis. TATA-box-binding protein (TBP), a general transcriptional factor (TF), couples with activators and chromatin remodelers to sustain the transcriptional activity of target genes. Here, we investigate the key role of TBP in HCC metastasis. METHODS: TBP expression was measured by PCR, western blot, and immunohistochemistry. RNA-sequencing was performed to identify downstream proteins. Functional assays of TBP and downstream targets were identified in HCC cell lines and xenograft models. Luciferase reporter and chromatin immunoprecipitation assays were used to demonstrate the mechanism mediated by TBP. RESULTS: HCC patients showed high expression of TBP, which correlated with poor prognosis. Upregulation of TBP increased HCC metastasis in vivo and in vitro, and muscleblind-like-3 (MBNL3) was the effective factor of TBP, positively related to TBP expression. Mechanically, TBP transactivated and enhanced MBNL3 expression to stimulate exon inclusion of lncRNA-paxillin (PXN)-alternative splicing (AS1) and, thus, activated epithelial-mesenchymal transition for HCC progression through upregulation of PXN. CONCLUSIONS: Our data revealed that TBP upregulation is an HCC enhancer mechanism that increases PXN expression to drive epithelial-mesenchymal transition.

Recent insights into function, structure and modification of cytochrome P450 153 a family.

Cytochrome P450 153 A (CYP153A) is a versatile enzyme that can catalyze a wide range of oxidation reactions on various substrates. This review provides a comprehensive overview of the current state of knowledge on CYP153A, including its classification, structure, function, and potential applications in biotechnology and pharmaceuticals. The CYP153A family encompasses many enzymes with different functions on a variety of substrates. We also discuss the structural features that are responsible for the different substrate specificities. Additionally, the enzyme has been engineered to increase its catalytic activity and modifications have been made to enhance its properties further. Despite its potential, challenges and limitations associated with studying and exploiting CYP153A remain, such as low expression levels and substrate inhibition. Nonetheless, ongoing research is exploring new ways to harness the enzyme's capabilities, particularly in synthetic biology, biocatalysis, and drug discovery, making it an exciting target for future research.

TAF15 exacerbates nonalcoholic steatohepatitis progression by regulating lipid metabolism and inflammation via FASN and p65 NF-κB.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) consists of a broad spectrum of conditions, and nonalcoholic steatohepatitis (NASH) is the advanced form of NAFLD. TAF15 is a DNA and RNA binding protein and is involved in crucial inflammatory signalling pathways. We aimed to investigate the role of TAF15 in the progression of NASH and the underlying molecular mechanism. METHODS: We generated mice with hepatocyte-specific knockdown and overexpression of TAF15 using a specific adeno-associated virus (AAV). NASH models were established by feeding mice high-fat and high-cholesterol diets and methionine- and choline-deficient diets. Cleavage under targets and tagmentation and dual-luciferase reporter assays were performed to investigate the effect of TAF15 on FASN transcription. Coimmunoprecipitation and immunofluorescence assays were conducted to explore the interaction of TAF15 and p65. In vitro coculture systems were established to study the interactions of hepatocytes, macrophages and HSCs. RESULTS: TAF15 was significantly increased in the livers of mouse NASH models and primary hepatocyte NASH model. Knockdown of TAF15 inhibited steatosis, inflammation and fibrosis, while overexpression of TAF15 promoted NASH phenotypes. Mechanistically, TAF15 bound directly to the promoter region of FASN to facilitate its expression, thereby promoting steatosis. Moreover, TAF15 interacted with p65 and activated the NF-κB signalling pathway, increasing the secretion of proinflammatory cytokines and triggering M1 macrophage polarization. Treatment with the FASN inhibitor orlistat partially reversed the phenotypes. CONCLUSIONS: These results suggested that TAF15 exacerbated NASH progression by regulating lipid metabolism and inflammation via transcriptional activation of FASN and interacting with p65 to activate the NF-κB signalling pathway.

HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a specific interaction with the PEDV S protein, and positive regulation of PEDV infection was validated by knockdown and overexpression tests. Further studies verified the role of HSPA5 in viral attachment and internalization. In addition, we found that HSPA5 interacts with S proteins through its nucleotide-binding structural domain (NBD) and that polyclonal antibodies can block viral infection. In detail, HSPA5 was found to be involved in viral trafficking via the endo-/lysosomal pathway. Inhibition of HSPA5 activity during internalization would reduce the subcellular colocalization of PEDV with lysosomes in the endo-/lysosomal pathway. Together, these findings show that HSPA5 is a novel PEDV potential target for the creation of therapeutic drugs. IMPORTANCE PEDV infection causes severe piglet mortality and threatens the global pig industry. However, the complex invasion mechanism of PEDV makes its prevention and control difficult. Here, we determined that HSPA5 is a novel target for PEDV which interacts with its S protein and is involved in viral attachment and internalization, influencing its transport via the endo-/lysosomal pathway. Our work extends knowledge about the relationship between the PEDV S and host proteins and provides a new therapeutic target against PEDV infection.

The menstrual cycle regularity and skin: irregular menstrual cycle affects skin physiological properties and skin bacterial microbiome in urban Chinese women.

BACKGROUND: The regularity of the menstrual cycle directly affects women's health. Many studies have focused on menstrual health; however, menstrual cycle regularity-related variations in skin physiological characteristics and skin microbiota have been seldom investigated. METHODS: To investigate the menstrual cycle regularity-related variations in skin physiological characteristics and skin microbiota of 197 cases of Chinese women aged 18-35 years living in shanghai in 2021. Based on a self-evaluation questionnaire, the volunteers were divided into three groups C1 (those with a regular menstrual cycle), C2 (those with a less regular menstrual cycle) and C3 (those with an irregular menstrual cycle). The physiological parameters of facial skin were measured by non-invasive methods and the skin microbiome was analyzed by 16S rRNA high-throughput sequencing. RESULTS: In the C3 group, the hydration content was significantly decreased (p < 0.05), the TEWL was significantly increased (p < 0.05), and the sebum content was increased (p > 0.05), indicating that the skin barrier integrity weakened with increased menstrual cycle irregularity. Additionally, the melanin level, L value and b value were significantly decreased (p < 0.05) in the C3 group, but the a value was significantly increased (p < 0.001), which indicated that the skin color became darker. Furthermore, the skin microbiota diversity decreased with increasing cycle irregularity, but the differences were not significant. The skin microbiota composition showed that the proportion of Firmicutes, Acinetobacter, Staphylococcus and Cutibacterium were increased in those with an irregular menstrual cycle, indicating that alterations in the ratio of bacterial phyla and/or genera might disturb skin homeostasis. Spearman correlation analysis revealed strong correlations between the microbiota and skin physiological parameters. Based on the associations among hormones, skin physiological parameters and skin microbiota, it is possible that the skin physiological parameters, as well as the skin microbial diversity and composition, change with hormonal fluctuations during the menstrual cycle. CONCLUSIONS: An irregular menstrual cycle can affect skin physiological characteristics and the skin microbiota. Female with an irregular menstrual cycle should strengthen skin care practices and use skin care products with moisturising and soothing effects to protect their skin.

Complete Genome Sequence of Staphylococcus capitis CCSM0123, Isolated from Healthy Facial Skin.

Staphylococcus capitis strain CCSM0123 was isolated from healthy facial skin. The complete genome of CCSM0123 was sequenced using a combination of Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) and Illumina sequencing. The assembled 2.5-Mbp genome consisted of one chromosome and four plasmids.

Complete Genome Sequence of Staphylococcus epidermidis CCSM0287, Isolated from Healthy Facial Skin.

Staphylococcus epidermidis strain CCSM0287 was isolated from healthy facial skin. The complete genome of CCSM0287 was sequenced using a combination of Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) and Illumina sequencing. The assembled 2.5-Mbp genome consisted of one chromosome and three plasmids.

The Characteristics of the Skin Physiological Parameters and Facial Microbiome of "Ideal Skin" in Shanghai Women.

Purpose: Everyone pursues perfect skin, but there exist significant differences between cultures, and no commonly accepted standards have been established. Therefore, our study attempted to define the "ideal skin" of oriental women and analyze the relationship between different skin physiological parameters and microbiomes. Patients and Methods: Based on our customized grading standard, the VISIA CR photos of 111 young women aged from 18 to 25 in Shanghai were collected and scored by the severity of pores, acne, spots, and wrinkles. The volunteers were then divided into "ideal skin" (W1), "normal skin" (W2), and "undesirable skin" (W3) groups. The physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiome was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: From "ideal skin" to "undesirable skin", the skin physiological parameters, α-diversity, and composition of the facial microbiome showed noticeable regular changes. Compared with the "normal skin" (W2) and "undesirable skin" (W3), the "ideal skin" (W1) group had lower sebum content, TEWL, melanin, hemoglobin, and roughness but higher hydration content and skin pH value. Furthermore, the Shannon index of skin bacteria was significantly increased in W1 (P = 0.004), suggesting that the ideal skin had higher species diversity. From W1 to W3, the species composition was changed significantly. The abundance of Actinobacteria was increased, while Proteobacteria and Bacteroidetes were decreased. Correspondingly, the abundances of lipophilic Propionibacterium and Malassezia were increased, while the abundances of Stenotrophomonas, Pseudomonas, Ralstonia, and Streptococcus, were significantly decreased. Additionally, Spearman correlation analysis revealed strong correlations between the physiological parameters and the microbiota. Notably, the Shannon index of skin bacteria was significantly positively correlated with skin hydration (P = 0.03) but negatively correlated with the abundance of Cutibacterium (P = 0.000), hemoglobin content (P = 0.025), and sebum content (P = 0.5). Therefore, the skin hydration content and the abundance of Cutibacterium played an important role in maintaining the α-diversity and skin homeostasis. Conclusion: Ideal skin had better water-oil balance and barrier function, higher microbial diversity, and more reasonable species distribution. Therefore, daily skincare needs to control skin oil and maintain skin microecological balance to achieve ideal skin conditions for young women aged 18-25 years old.

Lavender essential oil fractions alleviate sleep disorders induced by the combination of anxiety and caffeine in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavender (Lavandula angustifolia Mill.) essential oil is renowned for its use in the treatment of insomnia and mental disorder diseases in folk medicine. Previous pharmacological studies have also shown that lavender essential oil displays sedative and hypnotic activities. However, the active ingredients and mechanism of lavender essential oil for sleep-improving effect remain unclear. AIM OF THE STUDY: This study investigates whether inhalation of different fractions of lavender essential oil can attenuate the sleep disturbances induced by combined anxiety and caffeine and explores the underlying mechanisms. MATERIALS AND METHODS: Molecular distillation was applied to separate lavender essential oil into fractions containing different chemical components, and GC-MS was used to analyze the volatile compounds of lavender essential oil and its fractions. The elevated plus maze test, pentobarbital-induced sleep test, and neurotransmitters enzyme-linked immunosorbent assay were conducted to evaluate the anxiolytic and hypnotic effects of lavender essential oil and its fractions on mice suffering from sleep disorders. RESULTS: The results of behavioral tests indicated that lavender essential oil and its fractions (3%, v/v) exerted an ameliorating effect on sleep disturbances induced by anxiety and caffeine. The light fraction and heavy fractions exhibited complementary chemical composition, with the former enriched in linalool and trans-ß-ocimene and the latter in linalyl acetate, lavandulyl acetate, trans-caryophyllene, etc. The light fraction contributed more to sleep maintenance, and the heavy fraction performed better at sleep initiation. The neurobiological parameters elucidated that the mechanism of lavender essential oil for sleep-improving was multifaceted, related to the GABAergic system, cholinergic system, histaminergic system, and monoamines in the limbic system. The heavy fraction shared a similar mechanism with the lavender essential oil, while the light fraction did not actively participate in the cholinergic system, histaminergic system, and dopaminergic system. CONCLUSION: Taken together, our results demonstrated that different fractions of lavender essential oil played different roles in ameliorating sleep disorders, and this may be credited to their compositional differences and the complicated interactions with the central nervous system. The results are informative for future investigations on the molecular level mechanisms and provide guidance for appropriate applications of lavender essential oil.

In vitro and in silico analysis of 'Taikong blue' lavender essential oil in LPS-induced HaCaT cells and RAW264.7 murine macrophages.

BACKGROUND: 'Taikong blue' lavender, a space-bred cultivar of Lavandula angustifolia, is one of the main lavender essential oil production crops in Xinjiang Province, China. Several cases of local usage indicated that 'Taikong blue' lavender essential oil (TLEO) had excellent anti-inflammatory and antioxidant properties for skin problems. However, to date, substantial data on these functions are lacking. In this study, we aimed to investigate the composition and bioactivities of TLEO and the potential underlying mechanisms through LPS-induced inflammatory models of HaCaT and RAW264.7 cells. METHODS: The composition of TLEO was determined by GC‒MS. To study the anti-inflammatory and antioxidative properties of TLEO, we induced HaCaT and RAW264.7 cells by LPS. TLEO (0.001%-0.1%, v/v) was used to treat inflamed cells with dexamethasone (DEX, 10 µg/mL) as the standard drug. A variety of tests were carried out, including biochemical assays, ELISA, RT‒PCR, and western blotting. Docking of components was performed to predict potential ligands. RESULTS: The GC‒MS analysis revealed that 53 compounds (> 0.01%) represented 99.76% of the TLEO, and the majority of them were esters. TLEO not only reduced the levels of oxidative stress indicators (NO, ROS, MDA, and iNOS at the mRNA and protein levels) but also protected the SOD and CAT activities. According to the RT‒PCR, ELISA, and Western blot results, TLEO decreased inflammation by inhibiting the expression of TNF-α, IL-1ß, IL-6, and key proteins (IκBα, NF-кB p65, p50, JNK, and p38 MAPK) in MAPK-NF-кB signaling. Molecular docking results showed that all of the components (> 1% in TLEO) were potent candidate ligands for further research. CONCLUSION: The theoretical evidence for TLEO in this study supported its use in skin care as a functional ingredient for cosmetics and pharmaceutics.