pH-Responsive Wound Dressing Based on Biodegradable CuP Nanozymes for Treating Infected and Diabetic Wounds.

Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity. When examining acute infected wounds characterized by a low pH environment, the engineered Alg/CuP composite hydrogels demonstrated high bacterial eradication efficacy against both planktonic bacteria and biofilms, attributed to the combined action of catalytically generated hydroxyl radicals and the sustained release of Cu ions. In contrast, when applied to chronic diabetic wounds, which typically have a high pH environment, these composite hydrogels exhibit significant angiogenic performance. This is driven by the provision of catalytically generated dissolved oxygen and a beneficial supplement of Cu ions released from the degradable CuP nanozyme. Further, a mild thermal effect induced by NIR irradiation amplifies the catalytic activities and bioactivity of Cu ions, thereby enhancing the healing process of both infected and diabetic wounds. Our study validates that the synergistic integration of photothermal effects, catalytic activity, and released Cu ions can concurrently yield high antibacterial efficiency and tissue regenerative activity, rendering it highly promising for various clinical applications in wound healing.

Identification of Bioactive Compounds and Potential Mechanisms of Kuntai Capsule in the Treatment of Polycystic Ovary Syndrome by Integrating Network Pharmacology and Bioinformatics.

Objective: This study elucidates the potential therapeutic targets and molecular mechanisms of KTC in the treatment of PCOS. Materials and Methods: Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the active ingredients and potential targets of KTC were obtained. The Gene Expression Omnibus (GEO) database was used to find differentially expressed genes (DEGs) related to PCOS. Search the CTD, DisGeNet, genecards, NCBI, OMIM, and PharmGKB databases for therapeutic targets related to PCOS. The intersection of potential targets, DEGs, and therapeutic targets was submitted to perform bioinformatics analysis by R language. Finally, the analyses' core targets and their corresponding active ingredients were molecularly docked. Results: 88 potential therapeutic targets of KTC for PCOS were discovered by intersecting the potential targets, DEGs, and therapeutic targets. According to bioinformatics analysis, the mechanisms of KTC treatment for PCOS could be linked to IL-17 signaling route, p53 signaling pathway, HIF-1 signaling pathway, etc. The minimal binding energies of the 5 core targets and their corresponding ingredients were all less than -6.5. Further research found that quercetin may replace KTC in the treatment of PCOS. Discussion and Conclusions. We explored the active ingredients and molecular mechanisms of KTC in the treatment of PCOS and found that quercetin may be the core ingredient of KTC in the treatment of PCOS.

Bioactive NIR-II Light-Responsive Shape Memory Composite Based on Cuprorivaite Nanosheets for Endometrial Regeneration.

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near-infrared (NIR-II) light-responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4 O10 ) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l-lactide-co-trimethylene carbonate) (PT) as shape memory building blocks is developed. The as-prepared CUP/PT composite possesses excellent shape memory performance under NIR-II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy.

OBJECTIVE: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. METHODS: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper. RESULTS: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. CONCLUSIONS: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

Biofilm Formation of Candida albicans Facilitates Fungal Infiltration and Persister Cell Formation in Vaginal Candidiasis.

BACKGROUND: Vaginal candidiasis is an important medical condition awaiting more effective treatment. How Candida albicans causes this disease and survives antifungal treatment is not yet fully understood. This study aimed to establish a comprehensive understanding of biofilm-related defensive strategies that C. albicans uses to establish vaginal candidiasis and to survive antifungal treatment. METHODS: A mouse model of vaginal candidiasis was adopted to examine the formation of biotic biofilms on the vaginal epithelium and fungal infiltration by laboratory and clinical strains of C. albicans. Histopathological changes and local inflammation in the vaginal epithelium caused by C. albicans of different biofilm phenotypes were compared. Antifungal susceptibility testing was carried out for C. albicans grown as planktonic cells, microplate-based abiotic biofilms, and epithelium-based biotic biofilms. Formation of persister cells by C. albicans in different growth modes was also quantified and compared. RESULTS: C. albicans wild-type reference strains and clinical isolates, but not the biofilm-defective mutants, formed a significant number of biotic biofilms on the vaginal epithelium of mice and infiltrated the epithelium. Biofilm formation and epithelial invasion induced local inflammatory responses and histopathological changes in the vaginal epithelium including neutrophil infiltration and subcorneal microabscesses. Biofilm growth on the vaginal epithelium also led to high resistance to antifungal treatments and promoted the formation of antifungal-tolerant persister cells. CONCLUSION: This study comprehensively assessed biofilm-related microbial strategies that C. albicans uses in vaginal candidiasis and provided experimental evidence to support the important role of biofilm formation in the histopathogenesis of vaginal candidiasis and the recalcitrance of the infection to antifungal treatment.

SNHG5 enhances Paclitaxel sensitivity of ovarian cancer cells through sponging miR-23a.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies throughout the world. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been reported to play an important role in several human cancers, but the role of SNHG5 in the chemoresistance of ovarian cancer cells is yet elusive. METHOD: The expression of SNHG5 and miR-23a were determined by quantitative reverse transcriptase polymerase chain reaction. The effects of SNHG5 and miR-23a on the sensitivity of ovarian cancer cells to paclitaxel (PTX) were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. The subcellular location of SNHG5 was detected by a subcellular fraction assay. The interaction between SNHG5 and miR-23a was determined by luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: The expression of SNHG5 was downregulated in the cancer genome atlas cohort. Similarly, decreased expression of SNHG5 was observed in ovarian cancer tissues. Moreover, lower expression of SNHG5 was found in PTX-resistant ovarian cancer patients as well as PTX-resistant ovarian cancer cell lines. Downregulation of SNHG5 expression was indicative of poor prognosis in patients with ovarian cancer. Overexpression of SNHG5 enhanced the sensitivity of SKOV3/PTX and HeyA-8/PTX cells to PTX in vitro and enhanced PTX sensitivity in tumors in vivo. Interestingly, an inverse correlation between SNHG5 and miR-23a expression was found in ovarian cancer tissues and SNHG5 functioned as a decoy for miR-23a. Silencing of miR-23a overcame the resistance of SKOV3/PTX and HeyA-8/PTX cells to PTX. More importantly, miR-23a overexpression could reverse the inductive effect of SNHG5 overexpression on PTX sensitivity of ovarian cancer cells. CONCLUSION: SNHG5 enhanced the sensitivity of ovarian cancer cells to PTX through sponging miR-23a, providing a new mechanism of chemoresistance in ovarian cancer.

Maternal high-fat diet impairs follicular development of offspring through intraovarian kisspeptin/GPR54 system.

BACKGROUND: Excessive gestational weight gain (GWG), which is associated with adverse long-term effects on the health of the offspring, has become a major clinical problem. Accumulating evidence indicates that the ovary kisspeptin/GPR54 system directly participates in a series of physiological activities. We used a model of high-fat diet (HFD) during gestational to investigate offspring's ovarian function and whether kisspeptin/GPR54 system is involved. METHODS: After introducing the male and confirmation of mating by checking a vaginal sperm plug, female rats were randomized into two groups: control diet called NCD group and high-fat diet called HFD group. After birth, all rats were changed into a control diet and litter size was adjusted to 12 pups per litter. Ovaries were collected for assessment at postnatal day (PND) 4 and PND 30. The timing of vaginal opening was recorded, and the estrous cyclicity was monitored for 2 consecutive weeks immediately. Primary granulosa cells and ovaries which were taken from PND 4 were collected for determination of the direct effect of kisspeptin-10 (kp-10) in vitro. RESULTS: Neonatal rats exposed to HFD during gestation had a lower number of secondary follicles in the ovary. The expression of follicle-stimulating hormone receptor (FSHR) and kisspeptin was not altered. At prepuberty, the number of antral follicles and preovulatory follicles was elevated with decreased type III follicles in the HFD group. While the expression of ovulation-related genes was decreased, the expression levels of follicular growth-related genes and steroidogenesis synthesis related genes were elevated. A significant increase in kiss1 mRNA and kisspeptin protein was detected without changes in kiss1r mRNA and GPR54. Maternal high-fat diet during gestation resulted in a significant advanced puberty onset and an irregular estrous cycle in offspring rats. In addition, the administration of kp-10 produced an increase in viability of primary granulosa cells and enlarged the size of oocytes. CONCLUSIONS: HFD exposure during maternal gestation had a long-term effect on reproductive function in the offspring and the increased ovarian kisspeptin/GPR54 system might be involved.