Symbiotic combination of Akkermansia muciniphila and inosine alleviates alcohol-induced liver injury by modulating gut dysbiosis and immune responses.

Background: Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the therapeutic potential of combining Akkermansia muciniphila (A. muciniphila) with inosine in alleviating alcohol-induced liver injury. Methods: Male C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses. Results: Compared to the model group, the A. muciniphila and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the A. muciniphila and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria (Oscillibacter, Escherichia/Shigella, and Alistipes) induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by A. muciniphila combined with inosine treatment. Moreover, A. muciniphila and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4+CD39+Treg and CD4+CD73+Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the A. muciniphila and inosine combination on liver injury in ALD mice. Conclusion: This study reveals that the combination of A. muciniphila and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent.

Re-tear after arthroscopic rotator cuff repair can be predicted using deep learning algorithm.

The application of artificial intelligence technology in the medical field has become increasingly prevalent, yet there remains significant room for exploration in its deep implementation. Within the field of orthopedics, which integrates closely with AI due to its extensive data requirements, rotator cuff injuries are a commonly encountered condition in joint motion. One of the most severe complications following rotator cuff repair surgery is the recurrence of tears, which has a significant impact on both patients and healthcare professionals. To address this issue, we utilized the innovative EV-GCN algorithm to train a predictive model. We collected medical records of 1,631 patients who underwent rotator cuff repair surgery at a single center over a span of 5 years. In the end, our model successfully predicted postoperative re-tear before the surgery using 62 preoperative variables with an accuracy of 96.93%, and achieved an accuracy of 79.55% on an independent external dataset of 518 cases from other centers. This model outperforms human doctors in predicting outcomes with high accuracy. Through this methodology and research, our aim is to utilize preoperative prediction models to assist in making informed medical decisions during and after surgery, leading to improved treatment effectiveness. This research method and strategy can be applied to other medical fields, and the research findings can assist in making healthcare decisions.

Nano selenium-doped TiO2 nanotube arrays on orthopedic implants for suppressing osteosarcoma growth.

Osteosarcoma, the most common primary malignant bone tumor, is characterized by malignant cells producing osteoid or immature bone tissue. Most osteosarcoma patients require reconstructive surgery to restore the functional and structural integrity of the injured bone. Metal orthopedic implants are commonly used to restore the limb integrity in postoperative patients. However, conventional metal implants with a bioinert surface cannot inhibit the growth of any remaining cancer cells, resulting in a higher risk of cancer recurrence. Herein, we fabricate a selenium-doped TiO2 nanotube array (Se-doped TNA) film to modify the surface of medical pure titanium substrate, and evaluate the anti-tumor effect and biocompatibility of Se-doped TNA film. Moreover, we further explore the anti-tumor potential mechanism of Se-doped TNA film by studying the behaviors of human osteosarcoma cells in vitro. We provide a new pathway for achieving the anti-tumor function of orthopedic implants while keeping the biocompatibility, aiming to suppress the recurrence of osteosarcoma.

Enhanced efficiency of calcium-derived oleoyl serine on osteoporosis via Wnt/ß-catenin pathway.

Osteoporosis is a common disease of the elderly that affects millions of patients worldwide. It is mainly characterized by low bone mineral density and increased risk of fracture due to the deterioration of the bone structure, leading to difficulties in functional recovery, reduced quality of life, increased disability risk and mortality in the population. It has already been a major public health problem. Osteoporosis is a chronic disease that is difficult to treat in the elderly population, so it is crucial to develop new drugs for the treatment of osteoporosis. Oleoyl serine, an endogenous fatty acyl amide found in bone, has been shown to have excellent anti-osteoporosis effects, but it is easily hydrolyzed by amidases in vivo. The aim of this study is to determine the anti-osteoporotic effect of calcium-derived oleoyl serine, a novel oleoyl serine derivative and the molecular mechanism underneath. In vitro experiments demonstrated that calcium-derived oleoyl serine suppressed the expression of Fabp4, and Cebpα while Alp, and Runx2 was significantly upregulated compared with the oleoyl serine group and control. With the activation of ß-catenin, calcium-derived oleoyl serine restored the abnormal osteogenesis and lipogenesis, indicating calcium-derived oleoyl serine compared with oleoyl serine has better effects on promoting osteogenesis and suppressing lipogenesis. In vivo experiment agreed with these findings that calcium-derived oleoyl serine promotes osteogenesis and suppresses its lipogenesis to ameliorate osteoporosis via a ß-catenin dependent method. It is a new candidate for treating osteoporosis.

A study of the growth mechanism of large-diameter double-wall TiO2 nanotube arrays fabricated by high voltage anodization.

Background: Research on the growth mechanism of titanium dioxide (TiO2) nanotube arrays fabricated by anodic oxidation is essential to achieve artificial control of the microstructure and to expand their applications. In our previous work, we reported the preparation of highly ordered large-diameter double-wall TiO2 nanotube arrays prepared by high voltage anodization. Methods: In this paper, we observed and analyzed the initial growth process of large-diameter double-wall TiO2 nanotube arrays anodized at 120 V in ethylene glycol electrolyte containing aluminum fluoride (NH4F) and water (H2O), such as the evolution of surface and cross-sectional morphologies, the influence of current density on growth rate, the transition process from nanoholes to nanotubes, and the evolution of dimples on the remaining substrate. Results: On the basis of our observations and inspirations from the existing viewpoints, we established growth models of large-diameter double-wall TiO2 nanotube arrays corresponding to different growth stages to explain the growth process. The growth rate of anodic oxide film changes accordingly with the current density. The compact anodic oxide film formed initially actually contains outer layer and inner layer, with no obvious interface between them. Then, the bottom even levels of the inner layer and outer layer bulge towards the substrate and become individual hemisphere-like structures. The inner layer becomes the outer wall, and the outer layer becomes inner wall. Eventually, V-shaped large-diameter and double-wall TiO2 nanotube arrays form. Conclusions: The results presented in this work are significant and provide a better understanding of the growth mechanism of large-diameter double-wall TiO2 nanotube arrays anodized by high voltage.

Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications.

Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.

Long-term application of hydroxychloroquine could not prevent the infection of COVID-19.

INTRODUCTION: Current pandemic of the coronavirus induced disease 2019 (COVID-19) presents an urgent issue to the world due to lack of vaccine and medication. Hydroxychloroquine (HCQ) has generated a lot of controversies whether it is effective in prevention and treatment of COVID-19. Current report presents a 63-year-old woman who has taken HCQ for many years but still infected by COVID-19. CASE PRESENTATION: A patient with rheumatoid arthritis came to the clinic with fever and sore throat. The patient has been treated with 200 mg HCQ per day since 2016. Laboratory tests showed that the patient had lymphopenia, increased levels of high-sensitive C-reactive protein (hs-CRP) and serum Interleukin-6 (IL-6). Chest radiography showed that the patient had pneumonia. Throat swab test confirmed COVID-19 positive. On admission, she was treated with nebulized interferon alfa-2b, oral Lopinavir/Ritonavir, and ceftriaxone sodium for the COVID-19 in addition to HCQ. The patient stayed in hospital for 18 days, recovered from oxygen intake, and eventually discharged from hospital. Follow up investigation showed the patient developed antibody against COVID-19. CONCLUSIONS: Long-term application of HCQ could not prevent COVID-19 infection, but whether HCQ exerts benefit to alleviation of clinical symptoms and duration of hospital stays remains to be further investigated.

[Study of therapeutic effect and mechanism of Sihuang powder treating acute synovitis in experimental rabbit induced by papain injection].

OBJECTIVE: To prove the therapeutic effects of Sihuang powder (composed by four traditional Chinese herbs: root of baikal skullcap, bark of amur corktree, root of sorrel rhubarb, fruit of cape jasmine, which were mixed with wild Chrysanthemum flower solution)in treating acute synovitis in experimental rabbit knee osteoarthritic models induced by papain injection and to explore its mechanism. METHODS: Thirty-two New-Zealand white rabbits were divided into 6 groups: blank group, model group, Sihuang powder with high dosage group (2 g/kg), Sihuang powder with low dosage group (1 g/kg), Yingtaiqing group and wild Chrysanthemum flower group. The latter four groups were treated respectively with low and high dose Sihuang powder synovium and cartilage were tested concentrations of nitrogen monoxide (NO) and IL-1 level and then were prepared for pathologic and histologic observation 10 days later. Cartilage pathologic changes were record and synovium pathologic changes were valued by means of Mankin's value system. RESULTS: The NO concentration of synovium in Sihuang powder with high dosage group was lower than that of model group, and there was significantly differences between the two groups (P < 0.01). The IL-1 level of synovium was failed after treated with Sihuang powder with high dosage (P < 0.05). Sihuang powder with low dosage and Yingtaiqing also could restrain IL-1's release (P < 0.05). In Mankin's value system, Sihuang powder with high dosage almost eliminated inflammatory cells infiltrating in synovium, which was seldom found in other groups. The value of Sihuang powder with high dosage group was the lowest in treatment groups (P < 0.005). Sihuang powder with low dosage group and wild Chrysanthemum flower group also decreased the degree of inflammatory in synovium (P < 0.05). CONCLUSION: Sihuang powder can reduce the concentration of NO and IL-1 and improve inflammatory cell infiltrate in lining cells of synovium. Moreover, it can alleviate swelling and pain of joint, improve joint movement and postpone degeneration of the cartilage.