Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Molecular Mechanisms and Roles of MiR-136-5p in Human Cancer and Other Disorders.

BACKGROUND: MiR-136-5p plays a vital function in regulating developmental processes as well as in the pathophysiology of diseases, with a notable record in tumor suppression. METHODS: This article summarizes the latest findings on the physiological and pathophysiological processes of miR-136-5p in diseases. We searched for relevant studies and selected research articles from the last five years on PubMed with miR-136-5p as the keyword. RESULTS: MiR-136-5p represents a class of microRNAs (miRNAs) that are involved in various human maladies, encompassing cancers, cardio-cerebrovascular disease, diabetes, inflammatory disease, tuberous sclerosis, idiopathic pulmonary fibrosis, and polycystic ovary syndrome. Altered expression of miR-136-5p in specific ailments results in downstream gene expression imbalance, influencing cellular behaviors, such as migration, proliferation, and invasion. Furthermore, miR-136-5p is implicated in five signaling pathways, where it is critical in the onset and advancement of a number of illnesses. Additionally, it has the potential to promote drug resistance to a variety of medications. CONCLUSION: The current review aims to elucidate the role of miR-136-5p in both cancer progression and non-cancerous disorders, emphasizing dysregulated signaling pathways. It also sheds light on the potential of this miRNA as a prognostic biomarker in cancer, offering valuable insights and directions for future research.

Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Assessment of aortic hemodynamics in patients with thoracoabdominal aortic aneurysm using four-dimensional magnetic resonance imaging: a cross-sectional study.

Background: Thoracoabdominal aortic aneurysms (TAAAs) are rare but complicated aortic pathologies that can result in high morbidity and mortality. The whole-aorta hemodynamic characteristics of TAAA survivors remains unknown. This study sought to obtain a comprehensive view of flow hemodynamics of the whole aorta in patients with TAAA using four-dimensional flow (4D flow) magnetic resonance imaging (MRI). Methods: This study included patients who had experienced TAAA or abdominal aortic aneurysm (AAA) and age- and sex-matched volunteers who had attended China Hospital from December 2021 to December 2022 in West. Patients with unstable ruptured aneurysm or other cardiovascular diseases were excluded. 4D-flow MRI that covered the whole aorta was acquired. Both planar parameters [(regurgitation fraction (RF), peak systolic velocity (Vmax), overall wall shear stress (WSS)] and segmental parameters [pulse wave velocity (PWV) and viscous energy loss (VEL)] were generated during postprocessing. The Student's t-test or Mann-Whitney test was used to compare flow dynamics among the three groups. Results: A total of 11 patients with TAAA (mean age 53.2±11.9 years; 10 males), 19 patients with AAA (mean age 58.0±11.7 years; 16 males), and 21 controls (mean age 55.4±15.0 years; 19 males) were analyzed. The patients with TAAA demonstrated a significantly higher RF and lower Vmax in the aortic arch compared to healthy controls. The whole length of the aorta in patients with TAAA was characterized by lower WSS, predominantly in the planes of pulmonary artery bifurcation and the middle infrarenal planes (all P values <0.001). As for segmental hemodynamics, compared to controls, patients with TAAA had a significantly higher PWV in the thoracic aorta (TAAA: median 11.41 m/s, IQR 9.56-14.32 m/s; control: median 7.21 m/s, IQR 5.57-7.79 m/s; P<0.001) as did those with AAA (AAA: median 8.75 m/s, IQR 7.35-10.75 m/s; control: median 7.21 m/s, IQR 5.57-7.79 m/s; P=0.024). Moreover, a greater VEL was observed in the whole aorta and abdominal aorta in patients with TAAA. Conclusions: Patients with TAAA exhibited a stiffer aortic wall with a lower WSS and a greater VEL for the whole aorta, which was accompanied by a higher RF and lower peak velocity in the dilated portion of the aorta.

Systematic review and meta-analysis of endovascular therapy versus open surgical repair for the traumatic lower extremity arterial injury.

OBJECTIVE: For traumatic lower extremity artery injury, it is unclear whether it is better to perform endovascular therapy (ET) or open surgical repair (OSR). This study aimed to compare the clinical outcomes of ET versus OSR for traumatic lower extremity artery injury. METHODS: The Medline, Embase, and Cochrane Databases were searched for studies. Cohort studies and case series reporting outcomes of ET or OSR were eligible for inclusion. Robins-I tool and an 18-item tool were used to assess the risk of bias. The primary outcome was amputation. The secondary outcomes included fasciotomy or compartment syndrome, mortality, length of stay and lower extremity nerve injury. We used the random effects model to calculate pooled estimates. RESULTS: A total of 32 studies with low or moderate risk of bias were included in the meta-analysis. The results showed that patients who underwent ET had a significantly decreased risk of major amputation (OR = 0.42, 95% CI 0.21-0.85; I2=34%) and fasciotomy or compartment syndrome (OR = 0.31, 95% CI 0.20-0.50, I2 = 14%) than patients who underwent OSR. No significant difference was observed between the two groups regarding all-cause mortality (OR = 1.11, 95% CI 0.75-1.64, I2 = 31%). Patients with ET repair had a shorter length of stay than patients with OSR repair (MD=-5.06, 95% CI -6.76 to -3.36, I2 = 65%). Intraoperative nerve injury was just reported in OSR patients with a pooled incidence of 15% (95% CI 6%-27%). CONCLUSION: Endovascular therapy may represent a better choice for patients with traumatic lower extremity arterial injury, because it can provide lower risks of amputation, fasciotomy or compartment syndrome, and nerve injury, as well as shorter length of stay.

Upper extremity phlegmasia cerulea dolens complicating supra vena cava embolism in a cervical cancer patient: case report.

Phlegmasia cerulea dolens (PCD) is a rare yet severe complication of deep vein thrombosis (DVT), characterized by a high amputation rate and mortality. Early diagnosis and treatment are crucial in managing this condition. PCD predominantly affects the lower extremities rather than the upper extremities. We herein present a rare upper extremity PCD case accompanied with supra vena cava and pulmonary embolism in a cervical cancer patient, who presented to our institution with severe pain, edema and irreversible venous gangrene of right upper limb with no response to anticoagulation therapy. Emergency fasciotomy and amputation were performed due to the progressed venous gangrene, however, the patient developed severe infection and coagulation disorders, gastrointestinal bleeding and disseminated intravascular coagulation after the surgery. Despite medical interventions, her family chose to withdraw treatment and the patient died in ICU at the fourth day following emergency surgery.

[Research progress on development and utilization of minor ginsenosides].

Minor ginsenosides are a class of processed saponins with minor natural content, high bioavailability, and outstanding bio-logical activity, which are usually obtained by biological or chemical transformation of prototype saponins directly extracted from Panax plants. In recent years, with the clarification of the biosynthetic pathway of saponins and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce saponins. Minor ginsenosides have received widespread attention because of their remarkable biological activities in enhancing the immune function of the body and antitumor property. At present, most of the reviews on minor ginsenosides focus on transformation preparation, process optimization, and pharmacological activity, but there are some deficiencies in industrial analysis. This study summarized structural types, pharmacological activities, sources of acquisition, and transformation pathways of minor ginsenosides based on the relevant literature in China and abroad, proposed problems in the preparation of existing minor ginsenosides, and discussed the future research and utilization prospects, to provide a theoretical basis for improving the basic research of minor ginsenosides and promoting their industrialization.

miR-155-5p promotes hepatic steatosis via PICALM-mediated autophagy in aging hepatocytes.

BACKGROUND: Hepatic steatosis, a lipid disorder characterized by the accumulation of intrahepatic fat, is more prevalent in the elderly population. This study investigates the role of miR-155-5p in the autophagy dysregulation of aging hepatic steatosis. METHODS: We established an aging mouse model in vivo and a hepatocellular senescence model induced by low serum and palmitic acid in vitro. The fluctuations of microRNAs were derived from RNA-seq data and confirmed by qPCR in 4- and 18-month-old mouse liver tissues. Hematoxylin-eosin (H&E) staining observed pathological changes. Markers of senescence, autophagy, and lipolysis genes were analyzed using Western blot and qPCR. Bioinformatics analysis predicted miR-155-5p's target gene PICALM, confirmed by dual luciferase reporter assay and transfection of miR-155-5p mimic/inhibitor into senescent hepatocytes. RESULTS: Senescent markers (p21, p16, and p-P53) and miR-155-5p were up-regulated in aging liver tissues and senescent hepatocytes. Bioinformatics analysis identified PICALM as a target gene of miR-155-5p, a finding further supported by dual luciferase reporter assays. Inhibition of miR-155-5p reduced expression of senescent marker genes (p16, p21, p-P53), improved autophagy (evidenced by increased LC3B-II and ATG5, and decreased P62), and enhanced lipolysis (indicated by increased ATGL and p-HSL) in senescent hepatocytes. Oil red O staining confirmed that miR-155-5p inhibition significantly reduced lipid accumulation in these cells. CONCLUSIONS: This study suggests a potential new therapeutic approach for age-related hepatic steatosis through the inhibition of miR-155-5p to enhance autophagy.

Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem. METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION: This cell-based vascular graft is ready to undergo clinical trials for human patients.

The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition.

RAF, a core signaling component of the MAPK kinase cascade, is often mutated in various cancers, including melanoma, lung, and colorectal cancers. The approved inhibitors were focused on targeting the BRAFV600E mutation that results in constitutive activation of kinase signaling through the monomeric protein (Class I). However, these inhibitors also paradoxically activate kinase signaling of RAF dimers, resulting in increased MAPK signaling in normal tissues. Recently, significant attention has turned to targeting RAF alterations that activate dimeric signaling (class II and III BRAF and NRAS). However, the discovery of a potent and selective inhibitor with biopharmaceutical properties suitable to sustain robust target inhibition in the clinical setting has proven challenging. Herein, we report the discovery of exarafenib (15), a highly potent and selective inhibitor that intercepts the RAF protein in the dimer compatible αC-helix-IN conformation and demonstrates anti-tumor efficacy in preclinical models with BRAF class I, II, and III and NRAS alterations.

Gender Differences in Prognosis After Primary Resection for Retroperitoneal Liposarcoma.

BACKGROUND: Current evidence regarding gender difference in retroperitoneal liposarcoma (RLPS) is scarce, so we sought to investigate whether gender may affect prognosis after primary resection of RLPS. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify RLPS patients from January 1973 to December 2015. Multivariate cox proportional hazard analysis was adopted to generate adjusted hazard ratio (AHR) and 95% confidence intervals (CIs) of survival outcomes. RESULTS: In total, 2108 RLPS patients, including 971 women and 1137 men, were identified, with a median follow-up of 45.0 (17.0-92.0) months. The 5-year and 10-year overall survival rates were 50.5% and 31.5% for men and 60.4% and 42.5% for women. The 5-year and 10-year disease-specific survival rates for men and women were 71.5%, 57.3% and 76.3%, 62.1%, respectively. We found men were associated with an increased risk of all-cause mortality (AHR 1.3, 95% CI 1.0-1.6, P = .017) but not disease-specific mortality (AHR 1.2, 95% CI .9-1.6, P = .246). The subgroup analyses revealed that men were associated with an increased risk of all-cause mortality in patients with low-grade tumors (AHR 1.8, 95% CI 1.3-2.5) or patients who received non-radical resection (AHR 1.6, 95% CI 1.2-2.1). In the subgroup of low-grade tumors, men were also associated with an increased risk of disease-specific mortality (AHR 2.0, 95% CI 1.2-3.3). CONCLUSION: Men may have worse survival after primary resection of RLPS compared with women, especially in patients with low-grade tumors or patients who received non-radical resection. Gender-based disparities may deserve more attention in patients with RLPS.

2-Methoxyestradiol ameliorates paraquat-induced pulmonary fibrosis by inhibiting the TGF-ß1/Smad2/3 signaling pathway.

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-ß1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-ß1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.

LncRNA MEG3: Targeting the Molecular Mechanisms and Pathogenic causes of Metabolic Diseases.

BACKGROUND: Non-coding RNA is a type of RNA that does not encode proteins, distributed among rRNA, tRNA, snRNA, snoRNA, microRNA and other RNAs with identified functions, where the Long non-coding RNA (lncRNA) displays a nucleotide length over 200. LncRNAs enable multiple biological processes in the human body, including cancer cell invasion and metastasis, apoptosis, cell autophagy, inflammation, etc. Recently, a growing body of studies has demonstrated the association of lncRNAs with obesity and obesity-induced insulin resistance and NAFLD, where MEG3 is related to glucose metabolism, such as insulin resistance. In addition, MEG3 has been demonstrated in the pathological processes of various cancers, such as mediating inflammation, cardiovascular disease, liver disease and other metabolic diseases. OBJECTIVE: To explore the regulatory role of lncRNA MEG3 in metabolic diseases. It provides new ideas for clinical treatment or experimental research. METHODS: In this paper, in order to obtain enough data, we integrate and analyze the data in the PubMed database. RESULTS: LncRNA MEG3 can regulate many metabolic diseases, such as insulin resistance, NAFLD, inflammation and so on. CONCLUSION: LncRNA MEG3 has a regulatory role in a variety of metabolic diseases, which are currently difficult to be completely cured, and MEG3 is a potential target for the treatment of these diseases. Here, we review the role of lncRNA MEG3 in mechanisms of action and biological functions in human metabolic diseases.

Saponins from Panax japonicus improve neuronal mitochondrial injury of aging rats.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

miR-871-5p/PGC1α Regulates Aging-Induced Lipid Deposition in Hepatocytes Through Fatty Acid ß-Oxidation.

This study investigated the role of the miR-871-5p/proliferator-activated receptor α (PGC1α) pathway in ameliorating hepatic steatosis. We examined miR-871-5p expression in liver tissues of aging mice and AML12 senescent cells co-induced by low serum and palmitic acid (PA). Bioinformatics and multiple experiments were employed to validate the expression level of the target gene PGC1α for miR-871-5p. In this study, we aimed to investigate the potential role of miR-871-5p in regulating hepatic lipid deposition associated with aging. To do so, we performed in vitro transfection of both miR-871-5p mimic and inhibitor into senescent hepatocytes. Our results showed that miR-871-5p could inhibit PGC1α expression and cause lipid deposition in the liver due to aging. miR-871-5p controls this process by regulating PGC1α/fatty acid ß-oxidation. H&E staining displayed the appearance of fat vacuoles in the livers of aging mice, and fatty acid ß-oxidation-related genes (acyl-coenzyme A oxidase 1 carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor α) expression was significantly reduced. Lipogenic genes (sterol regulatory element binding protein 1C and fatty acid synthase) expression level was increased in the livers of aging mice. In AML12 cells co-induced by low serum and PA, miR-871-5p mimics decreased PGC1α expression and increased lipid droplet accumulation in senescent hepatocytes. Conversely, miR-871-5p inhibitor promoted PGC1α expression and reduced lipid deposition in senescent hepatocytes. Our findings suggest that inhibiting miR-871-5p could be crucial in ameliorating aging-associated hepatic steatosis. These findings offer valuable insights into the molecular mechanisms driving hepatic steatosis in aging.

ZNF671 methylation test in cervical scrapings for cervical intraepithelial neoplasia grade 3 and cervical cancer detection.

Effective triage of high-risk human papillomavirus (hrHPV)+ women is warranted to avoid unnecessary referral and overtreatment. Molecular triage tests have recently begun to impact cervical intraepithelial neoplasia grade 3 (CIN3) or cervical cancer (CC), termed CIN3+, detection. We find that zinc finger protein 671 methylation (ZNF671m) test has superior performance for CIN3+ detection in all single molecular triage tests, including HPV16/18 genotyping, paired box gene 1 methylation (PAX1m), and ZNF671m, in the training set. Using ZNF671m test instead of Thinprep cytologic test (TCT) as a single triage strategy or as a combined triage strategy with HPV16/18 genotyping has achieved comparable sensitivity but higher specificity for CIN3+ detection among 391 hrHPV+ women in the validation set. Little attention has been paid to the women with hrHPV- status but detected CIN3+. We find that the CIN3+ risk after a negative result could be reduced further by triage using ZNF671m in hrHPV- patients.

[The mechanism of microcystin leucine-arginine (MC-LR)-induced injury of Sertoli cell immune response and biological behavior].

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.

Hard and Soft Tissue Alterations After Immediate Implant Placement and Provisionalization with Customized Definite Abutment in Esthetic Zone: A Retrospective Study.

PURPOSE: To evaluate the hard and soft tissue alterations of immediate implant placement and provisionalization with customized definitive abutments in the esthetic zone. MATERIALS AND METHODS: Single unsalvageable maxillary anterior teeth were replaced with immediate implant placement and provisionalization with definitive abutments in 22 participants. Digital impressions and CBCT images were obtained presurgery, immediately after surgery, and 6 months after surgery. Horizontal and vertical buccal bone changes in thickness and height (HBBT, VBBH), vertical changes for the gingiva margin, mesial and distal papilla height, and horizontal changes for soft tissue (HCST) were analyzed using a 3D superimposition method. RESULTS: Twenty-two participants completed the study. No implant failed, and there were no mechanical or biologic complications for any patients. At 6 months after surgery, the mean HBBT changes at 0, 1, 2, 3, 5, 7, 10, 11.5, and 13 mm were -0.92 ± 0.73, -0.83 ± 0.53, -0.82 ± 0.49, -0.70 ± 0.64, -0.65 ± 0.47, -0.50 ± 0.51, -0.15 ± 0.45, -0.10 ± 0.57, and -0.00 ± 0.64 mm, respectively. The mean VBBH change was -0.61 ± 0.76 mm. The mean HCSTs at -3, -2, -1, 0, 1, 2, and 3 mm sub- and supra-implant shoulder were -0.65 ± 0.54, -0.70 ± 0.56, -0.65 ± 0.51, -0.61 ± 0.56, -0.47 ± 0.54, -0.47 ± 0.59, and -0.46 ± 0.59 mm, respectively. The mean gingiva margin recession was -0.38 ± 0.67 mm. The mean mesial papilla height recession was -0.03 ± 0.50 mm. The mean distal papilla height recession was -0.12 ± 0.56 mm. CONCLUSION: The definitive abutment used with immediate implant placement and provisionalization could potentially maintain the buccal bone thickness and height. For the facial soft tissue, it also benefited the maintenance of the midfacial gingival margin position and papilla height during the 6-month follow-up. Int J Oral Maxillofac Implants 2023;38:479-488. doi: 10.11607/jomi.9914.

Comprehensive analysis of the role of SFXN family in breast cancer.

The sideroflexin (SFXN) family is a group of mitochondrial membrane proteins. Although the function of the SFXN family in mitochondria has been widely recognized, the expression levels, role, and prognostic value of this family in breast cancer (BC) have not been clearly articulated and systematically analysed. In our research, SFXN1 and SFXN2 were significantly upregulated in BC versus normal samples based on Gene Expression Profiling Interactive Analysis 2 and the Human Protein Atlas databases. We found that high SFXN1 expression was significantly related to poor prognosis in BC patients and that high SFXN2 expression was significantly associated with good prognosis in BC patients. Gene Ontology analysis of the SFXN family was performed based on the STRING database to explore the potential functions of this family, including biological processes, cellular components, and molecular functions. Based on the MethSurv database, we found that two SFXN1 CpG sites (5'-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3'-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), and nine SFXN5 CpG sites (1stExon;5'-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. According to the ENCORI database, four negative regulatory miRNAs for SFXN1 (hsa-miR-22-3p, hsa-miR-140-5p, hsa-miR-532-5p, and hsa-miR-582-3p) and four negative regulatory miRNAs for SFXN2 (hsa-miR-9-5p, hsa-miR-34a-5p, hsa-miR-532-5p, and hsa-miR-885-5p) were related to poor prognosis for BC patients. This study suggests that SFXN1 and SFXN2 are valuable biomarkers and treatment targets for patients with BC.

Randomised controlled trial to evaluate the effect of contrast material dilution on renal function in patients after endovascular aortic repair: rationale and design for the CULTURE trial.

INTRODUCTION: Postoperative renal function decline is a major concern for thoracic endovascular aortic repair (TEVAR) and endovascular abdominal aortic repair (EVAR). Diluting contrast medium in the power injector may be helpful in reducing the risk of contrast-induced nephropathy, but it can also blur fluoroscopic vision during surgery. The quality of the current evidence is very low; thus, this study is designed to investigate the effect of contrast dilution in the power injector on renal function changes in patients after endovascular aortic repair. METHOD AND ANALYSIS: The study is a prospective, single-blind, parallel, non-inferiority, randomised controlled trial with two independent cohorts: Cohort TEVAR and EVAR. Individuals will enter the appropriate cohort based on clinical interviews if they meet the eligibility criteria. Participants in Cohort TEVAR and EVAR will be randomly allocated to the intervention group (diluting contrast medium to 50% in the power injector) and control group (pure contrast medium in the power injector) separately in a 1:1 ratio. The primary study points consist of the proportion of patients who develop acute kidney injury within 48 hours after TEAVR or EVAR (first stage) and freedom of major adverse kidney events at 12 months after TEAVR or EVAR (second stage). The safety endpoint is freedom of all types of endoleaks at 30 days after TEVAR or EVAR. Follow-up will be conducted at 30 days and 12 months after intervention. ETHICS AND DISSEMINATION: The trial was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (approval number: 20201290). The results of the study will be disseminated through publications in peer-reviewed journals and presentations at academic conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2100042555).