Dissecting the association between gut microbiota and hypertrophic scarring: a bidirectional Mendelian randomization study.

Hypertrophic scars affect a significant number of individuals annually, giving rise to both cosmetic concerns and functional impairments. Prior research has established that an imbalance in the composition of gut microbes, termed microbial dysbiosis, can initiate the progression of various diseases through the intricate interplay between gut microbiota and the host. However, the precise nature of the causal link between gut microbiota and hypertrophic scarring remains uncertain. In this study, after compiling summary data from genome-wide association studies (GWAS) involving 418 instances of gut microbiota and hypertrophic scarring, we conducted a bidirectional Mendelian randomization (MR) to investigate the potential existence of a causal relationship between gut microbiota and the development of hypertrophic scar and to discern the directionality of causation. By utilizing MR analysis, we identified seven causal associations between gut microbiome and hypertrophic scarring, involving one positive and six negative causal directions. Among them, Intestinimonas, Ruminococcus2, Barnesiella, Dorea, Desulfovibrio piger, and Ruminococcus torques act as protective factors against hypertrophic scarring, while Eubacterium rectale suggests a potential role as a risk factor for hypertrophic scars. Additionally, sensitivity analyses of these results revealed no indications of heterogeneity or pleiotropy. The findings of our MR study suggest a potential causative link between gut microbiota and hypertrophic scarring, opening up new ways for future mechanistic research and the exploration of nanobiotechnology therapies for skin disorders.

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Highly Bioactive MXene-M2-Exosome Nanocomposites Promote Angiogenic Diabetic Wound Repair through Reconstructing High Glucose-Derived Immune Inhibition.

The repair of diabetic wounds remains challenging, primarily due to the high-glucose-derived immune inhibition which often leads to the excessive inflammatory response, impaired angiogenesis, and heightened susceptibility to infection. However, the means to reduce the immunosuppression and regulate the conversion of M2 phenotype macrophages under a high-glucose microenvironment using advanced biomaterials for diabetic wounds are not yet fully understood. Herein, we report two-dimensional carbide (MXene)-M2 macrophage exosome (Exo) nanohybrids (FM-Exo) for promoting diabetic wound repair by overcoming the high-glucose-derived immune inhibition. FM-Exo showed the sustained release of M2 macrophage-derived exosomes (M2-Exo) up to 7 days and exhibited broad-spectrum antibacterial activity. In the high-glucose microenvironment, relative to the single Exo, FM-Exo could significantly induce the optimized M2a/M2c polarization ratio of macrophages by activating the PI3K/Akt signaling pathway, promoting the proliferation, migration of fibroblasts, and angiogenic ability of endothelial cells. In the diabetic full-thickness wound model, FM-Exo effectively regulated the polarization status of macrophages and promoted their transition to the M2 phenotype, thereby inhibiting inflammation, promoting angiogenesis through VEGF secretion, and improving proper collagen deposition. As a result, the healing process was accelerated, leading to a better healing outcome with reduced scarring. Therefore, this study introduced a promising approach to address diabetic wounds by developing bioactive nanomaterials to regulate immune inhibition in a high-glucose environment.

Nuciferine improves random skin flap survival via TFEB-mediated activation of autophagy-lysosomal pathway.

Due to their simplicity and reliability, random-pattern skin flaps are commonly utilized in surgical reconstruction to repair cutaneous wounds. However, the post-operative necrosis frequently happens because of the ischemia and high-level of oxidative stress of random skin flaps, which can severely affect the healing outcomes. Earlier evidence has shown promising effect of Nuciferine (NF) on preventing hydrogen peroxide (H2O2)-induced fibroblast senescence and ischemic injury, however, whether it can function on promoting ischemic flap survival remains unknown. In this work, using network pharmacology analysis, it was possible to anticipate the prospective targets of NF in the context of ischemia. The results revealed that NF treatment minimized H2O2-induced cellular dysfunction of human umbilical vein endothelial cells (HUVECs), and also improved flap survival through strengthening angiogenesis and alleviating oxidative stress, inflammation and apoptosis in vivo. These outcomes should be attributed to TFEB-mediated enhancement of autophagy-lysosomal degradation via the AMPK-mTOR signaling pathway, whilst the restriction of autophagy stimulation with 3MA effectively diminished the above advantages of NF treatment. The increased nuclear translocation of TFEB not only restored lysosome function, but also promoted autophagosome-lysosome fusion, eventually restoring the inhibited autophagic flux and filling the high energy levels. The outcomes of our research can provide potent proof for the application of NF in the therapy of vascular insufficiency associated disorders, including random flaps.

The prevalence and risk factors of different degrees of stress urinary incontinence in Chinese women: A community-based cross-sectional study.

AIM: To investigate the prevalence of SUI and explore the factors that could influence the severity of SUI in adult females. DESIGN: A cross-sectional study. METHODS: A total of 1178 subjects were assessed using a risk-factor questionnaires and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and then divided into no SUI group, mild SUI group and moderate-to-severe SUI group according to the ICIQ-SF score. Univariate analysis between adjacent groups and ordered logistic regression models in three groups were then performed to analysis the possible associated factor with the progressive of SUI. RESULTS: The prevalence of SUI among adult women was 22.2% of them; 16.2% and 6% had mild SUI and moderate-to-severe SUI, respectively. Moreover, logistic analysis revealed that age, BMI, smoking, position preference for urination, urinary tract infections, urinary leaks during pregnancy, gynaecological inflammation and poor sleep quality were independent risk for the severity of SUI. CONCLUSION: SUI symptoms were mostly mild among Chinese females, specific risk factors such as unhealthy living habits and urination behaviours increased the risk of SUI and the aggravation of symptoms. Therefore, targeted interventions should be formulated for women to delay disease progression.

Advances in the natural history of urinary incontinence in adult females.

The aim of this review is to summarise the related characteristics of the natural history of female urinary incontinence (UI) using a narrative descriptive approach. PubMed, EMBASE and Web of Science were searched for articles published from 1 January 2010 to 1 January 2020 on the natural history of female UI, which including incidence, persistence, progression, remission, and regression of a single subtype of UI and the mutual influence of different UI subtypes. This literature review includes 15 articles published, indicates that UI is highly dynamic, with symptoms varying according to disease severity and subtype and influenced by multiple factors at different disease stages. Recent studies have increased our understanding of the natural history of UI. Future research should systematically analyse the progression of each subtype of UI and interactions between subtypes to prevent the progression of UI across females life course.

Surface Modification of Bacteria to Optimize Immunomodulation for Advanced Immunotherapy.

Bacteria have been widely exploited as therapeutic agents for immunotherapy due to their native immunogenicity, living characteristic, and genetic manipulability. However, conventional bacteria-based immunotherapy often suffers from dose-dependent safety issues and poor treatment efficacy. Harnessing surface modification of bacteria to carry additional immune modulators has emerged as a promising strategy to reduce bacterial dose and synergistically enhance the activation of immune responses. In this paper, bacteria-mediated immunomodulation and the underlying mechanisms are introduced, followed by a summarization on the concept of using surface-modification approaches including physical encapsulation, chemical conjugation, and metabolic labelling to combine diverse immune functions. The applications of modified bacteria as therapeutics for immunotherapy toward cancer and inflammatory bowel disease have been expounded further. Both challenges and future perspectives regarding the utilization of surface-modified bacteria for immunomodulation are also proposed. This work offers unique insights into developing safe yet potent bacteria-based therapeutics for advanced immunotherapy.

MDL-800, the SIRT6 Activator, Suppresses Inflammation via the NF-κB Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase belonging to the sirtuin family. It has been shown to participate in wound healing and some inflammation-related disorders. However, the effect of MDL-800, a highly efficient and selective SIRT6 activator, on wound healing and inflammation has not been reported. Therefore, this study investigated whether MDL-800 confers anti-inflammatory effects and promotes wound healing and uncovered the molecular mechanisms involved. This was achieved using mouse models of full-thickness wounds. Results showed that MDL-800 significantly downregulated inflammation by attenuating the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds, thereby accelerating cutaneous wound healing. Furthermore, MDL-800 significantly downregulated expression levels of TNF-α and IL-6 in the dorsal skin tissue of mice via the NF-κB pathway. These results demonstrated that MDL-800 exerted anti-inflammatory and prohealing effects, indicating that the SIRT6/NF-κB/IκB signaling pathway may play an important role in wound healing.

Prevalence and associated factors of urinary incontinence in women living in China: a literature review.

BACKGROUND: This review of studies on urinary incontinence (UI) was focused primarily on UI prevalence rates and associated factors across the adult lifecourse of Chinese women. UI is a urologic symptom that can have a significant impact on women's physical and mental health and quality of life. In addition, women with UI may experience socioeconomic burdens due to UI's effect on their ability to work and function in society. Although researchers from many countries have reported prevalence rates and associated factors for UI, little is known about the prevalence of UI in China's large female population. Language may act as a barrier to the inclusion of published studies in English-language journals. To overcome this barrier and to add to the global knowledge base about UI in women, the authors reviewed and discussed findings from epidemiological studies published in China and in Chinese language. METHODS: The authors retrieved research studies from the Wanfang database using the following search terms: "Subject: (Female) × Subject: (Urinary incontinence) × Subject: (Prevalence) × Date: 2013 to 2019". Searches employed the China National Knowledge Infrastructure Database, VIP Database for Chinese Technical Periodicals and China Biology Medicine Database. The authors also used PubMed to search English-language studies published in Chinese journals on UI in Chinese women. RESULTS: This literature review includes 48 articles published between January 2013 and December 2019. The overall UI prevalence rates reported in adult Chinese women ranged from 8.7 to 69.8%, representing 43-349 million women, respectively. For women aged 17-40 years, 41-59 years, and 60 years and older, prevalence rates ranged from 2.6-30.0, 8.7-47.7, to 16.9-61.6%, respectively. Significant associated factors for overall UI included age, body mass index, constipation, parity, and menopause. Despite the 17-40 age range being peak reproductive years, the literature revealed little focus on UI prevalence rates. For women aged 41-59 years, the main associated factors included those related to pregnancy and gynecologic diseases. For women 60 years and older, chronic diseases represented most of the associated factors. CONCLUSIONS: About 43-349 million Chinese women may experience UI. Many of the identified associated factors could be mitigated to reduce UI incidence and prevalence rates. Little is known about the prevalence rates and associated factors for UI among young (aged 17-40) Chinese women. Future research should investigate UI in young women to improve bladder health across their lifecourse.

Toileting behaviors and factors associated with urinary incontinence in college-aged female students in China.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is prevalent among women, including young women (18-30 years old). This article aims to explore the prevalence of UI, as well as toileting behaviors and other factors that are associated with UI, in female college students in central China. METHODS: We used convenience sampling to recruit 1000 students from five institutions of higher education. We distributed pencil-and-paper questionnaires to obtain demographic, environmental, and general health information, including whether UI was present or not, and information regarding toileting behaviors used by the respondents. RESULTS: Most students, n = 929, responded to the questionnaire. Their ages ranged from 18 to 26 years old (average: 20.5 ± 1.6); 23.6% of these respondents reported UI, 52.7% often/always worried about public toilet cleanliness, and 25.3% often/always delayed emptying their bladder when they were busy. Respondents who were between 21 and 26 years old had a lower probability of UI (odds ratio [OR] = 0.867 and 95% confidence interval [CI] = 0.771-0.975) than younger respondents (18-21 years old). Respondents who reported constipation (OR = 2.395, 95% CI = 1.494-3.839), drank alcohol (OR = 1.763, 95% CI = 1.114-2.792), often/always delayed urination (OR = 1.738, 95% CI = 1.306-2.313), and/or often/always strained to urinate (OR = 1.433, 95% CI = 1.111-1.849) had greater odds of having UI than respondents who did not have constipation or engage in these behaviors. CONCLUSIONS: UI is prevalent in young Chinese women who are attending college. These women should be asked and given culturally appropriate information about UI and associated factors that include toileting behaviors.

Toileting Behaviors Related to Urination in Women: A Scoping Review.

This scoping review explores the state of science regarding women's toileting behaviors, gaps in knowledge, and areas for future research. Online databases were searched to identify papers published in English between January 2010 through July 2019; the search identified 25 articles. The Toileting Behaviors-Women's Elimination Behaviors scale has been published in four validated language versions and used in 17 of the 25 studies. The most frequent behaviors include concern about public toilet cleanliness, delaying urination when busy or away from home, and using different toileting postures at and away from home. Determinants of toileting behaviors include environmental factors, chronic health conditions, and cognitive/psychological factors. Associations were found between toileting behaviors and lower urinary tract symptoms and between toileting postures and uroflowmetric parameters and post-void residual volume. Strategies that address modifiable determinants of toileting behaviors should be developed and tested in future research. Furthermore, little is known about the toileting behaviors and bladder health in older women and women from developing countries. Rigorous studies are needed to better understand the underlying mechanisms of toileting behaviors, the nature of associations between toileting behaviors and lower urinary tract symptoms, and effects of the environment on women's toileting behaviors.

Changes of serum lipopolysaccharide, inflammatory factors, and cecal microbiota in obese rats with type 2 diabetes induced by Roux-en-Y gastric bypass.

OBJECTIVES: Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D. METHODS: Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; n = 8), diabetes sham operation (DS; n = 8), and diabetic control (DC; n = 8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; n = 8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups. RESULTS: Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D. CONCLUSIONS: Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.

Prevalence of lower urinary tract symptoms and associated distress among female college students in Xuzhou / 中国学校卫生

Objective@#To explore the prevalence and associated distress of lower urinary tract symptoms among female college students in Xuzhou.@*Methods@#Convenience sampling was used to recruit 1 000 female college students in Xuzhou China. Chinese versions of International Consultation on Incontinence Questionnaire LUTS and General Information Questionnaire was used.@*Results@#The prevalence of lower urinary tract symptoms was 95.7%. The top ten prevalence rates were urgency (88.2%), hesitancy (65.4%), nocturia (48.5%), intermittent stream (47.3%), straining (30.5%), increased daytime frequency (30.1%), bladder pain (21.0%), SUI (18.5%), UUI (13.9%), nocturnal enuresis (7.5%). Urinary urgency was the most disturbing symptom (49.0%). Risk factors of urinary urgency included rural household registration (OR=1.67, 95%CI:1.10-2.55, P=0.017) and premature urination (OR=1.65, 95%CI:1.23-2.21, P=0.00).@*Conclusion@#Female college students have a high prevalence of lower urinary tract symptoms but with moderate severity and distress. Toileting behaviors affect bladder health, which require early intervention.