NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

Thrombosis of acute superior mesenteric artery in a patient with breast cancer receiving toremifene therapy: a case report and literature review.

It is widely recognized that cancer itself is related to increased risk of thromembolism. Venous thromboembolism is relatively common in breast cancer patients, but arterial thrombosis, especially acute superior mesenteric artery thrombosis (SMAT) associated with chemotherapy or endocrinotherapy, rarely occurs in breast cancer patients. There were few reports about acute SMAT in cancer patients who underwent chemotherapy, but no reports of acute SMAT caused by endocrine-therapy. We reported a 54-year-old patient with acute SMAT during toremifene treatment after breast cancer surgery. She underwent 4 cycles chemotherapy of TC regimen, then accepted toremifen endocrinotherapy because of positive estrogen receptor. She suffered from acute SMAT after 2 months toremifen treatment. Therefore, we consider that this case of acute SMAT may be a rare adverse event of toremifen. In view of the high risk and rarity of acute SMAT caused by toremifene, we suggest that except for venous thrombosis, arterial thrombosis in special position (ATSP) should be kept in mind during use of toremifene. Once a thrombotic event occurs, toremifene should be stopped immediately.

Sequential mediation model of social support, care burden, and internalized stigma among family function and depression in caregivers of patients with schizophrenia: evidence from a cross-sectional study in southwest China.

PURPOSE: There is a lack of comprehensive measurements and systematic evaluations of the depression in caregivers of patients with psychiatric disorders and the factors influencing them in China. This study aims to explore the relationship between family function and depression in caregivers of patients with schizophrenia at the individual, family, and social levels according to the ecological system theory and attachment theory. METHODS: In this study, multi-stage, stratified cluster sampling was adopted to sample caregivers of patients with schizophrenia as subjects from one to three counties of four counties in Yunnan, from September 2022 to March 2023. Collecting the current caregiver's demographic data, family functions, social support, care burden, depression and internalized stigma. RESULTS: The results of single-factor analysis show that age, education level, relationship with patients, and the degree of self-care of patients are the influencing factors of depression of people living with schizophrenia (p < 0.05). The scores of self-rating depression scale are higher for caregivers who have not received formal education, caregivers who cannot take care of themselves and the parents, spouses and children of patients. The results of Pearson correlation analysis show that depression is positively associated with internalized stigma and care burden, and negatively associated with social support and family function (p < 0.05). The results of multiple linear regression show that after controlling age, education level, the patient's self-care capacity, and relationship with patient, the internalized stigma (ß = 0.184, p = 0.01) is positively correlated with depression. The mediation effect route of family function → social support → care burden → internalized stigma → depression was significant with 95% confidence interval [-0.150, -0.01], and the chained mediation effect was 5.904%. CONCLUSIONS: To reduce the depression level in family caregivers of schizophrenia, apart from taking measures to improve the caregiver's family function, enhancing social support, decreasing care burden, and reducing internalized stigma are suggested.

Rational design of the Z-scheme hollow-structure Co9S8/g-C3N4 as an efficient visible-light photocatalyst for tetracycline degradation.

The development of photocatalysts with high catalytic activity that are capable of full utilization of solar energy is a challenge in the field of photocatalysis. Accordingly, in the present study, an efficient Z-scheme cage-structured Co9S8/g-C3N4 (c-CSCN) photocatalyst was constructed for the degradation of tetracycline antibiotics under visible-light irradiation. The Z-scheme charge-transfer mechanism accelerates the separation of photogenerated charge carriers and effectively improves photocatalytic activity. Moreover, c-CSCN has a hollow structure, allowing light to be reflected multiple times inside the cavity, thereby effectively improving the utilisation efficiency of solar energy. As a result, the photocatalytic activity of c-CSCN is 1.5-, 2.5-, and 5.8-times higher than those of sheet-type Co9S8/g-C3N4 (s-CSCN), c-Co9S8, and g-C3N4, respectively, for the degradation of tetracycline. c-CSCN maintains favourable photocatalytic activity over five consecutive degradation cycles, demonstrating its excellent stability. In addition, c-CSCN performs efficient tetracycline removal in different water substrates. Moreover, c-CSCN exhibits excellent ability to remove tetracycline under direct natural sunlight. This work fully demonstrates that c-CSCN has high catalytic activity and the potential for practical application as a wastewater treatment material.

MiR-6869-5p Induces M2 Polarization by Regulating PTPRO in Gestational Diabetes Mellitus.

The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.

Implications of gender-based variabilities in bone mineral density and hemoglobin levels.

BACKGROUND: Studies reported that there is a relationship between volumetric bone mineral density (vBMD) and hemoglobin (HGB) in sickle cell anemia, chronic obstructive pulmonary disease, inflammatory bowel disease, and chronic kidney disease, it is not clear whether this association exists in normal populations or different genders. In order to further clarify the relationship between vBMD and HGB, and provide the basis for the diagnosis of related diseases, this study was conducted in the physical examination population. METHODS: A cross-sectional study was conducted on a health check-up population from Wannan area of China from January to December 2018. The study involved 1238 individuals aged 23 to 85 years. Linear regression analysis and smooth curve were applied to determine the relationship of HGB and vBMD. RESULTS: The average level of vBMD in the population was 130.11 ± 79.51 mg/cm3, after adjusting for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), glucose (GLU), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A U-shape relationship was established between vBMD and HGB, the cut off value of HGB was 130 g/L. After gender stratification, the results showed a U-shaped curve relationship between vBMD and HGB in male group, and a linear relationship between vBMD and HGB in female group. The vBMD decreased with HGB when HGB < 120 g/L, and increased when HGB ≥ 120 g/L in male group. CONCLUSION: The relationship between vBMD and HGB in the male physical examination population presents a U-shaped curve.

Three-Dimensional Computed Tomography Scan Analysis of Secondary Labial Deformities in Patients With Unilateral Cleft Lip/Cleft Palate After Revisional Surgery.

BACKGROUND: Surgical reconstruction of secondary labial deformities associated with isolated unilateral cleft lip (UCL) and/or UCL and palate (UCLP) is challenging. There have been few studies in the literature looking at labial soft tissues quantitatively to assess surgical results. OBJECTIVE: To apply a novel computer-aided, 3-dimensional reconstruction technique based on CT scan images to conduct quantitative preoperative and postoperative assessments in patients with UCL/UCLP undergoing surgical revision of secondary labial deformities. METHODS: Preoperative and postoperative spiral computed tomographic (CT) scans of the face were performed in 21 randomly selected UCL or UCLP patients, who underwent secondary lip revision surgery. The data was then imported to the SimPlant 11.04 software system. Fixed point-to-point, linear distance, and angles were measured, statistically analyzed and used to assess the effect of the surgery. RESULTS: Preoperative measurements showed that the thickness of the upper vermilion at the apex of the Cupid's bow on the affected side was greater than that on the unaffected side. The distance from the apex of the Cupid's bow to the ipsilateral subnasal point of the affected side was smaller than that of the unaffected side (P < 0.05). After surgery, the subjects were rescanned at an average of 9 months, and the curative effects were evaluated. The statistically significant preoperative differences between the affected and unaffected sides were not found postoperatively indicating surgical success. CONCLUSIONS: This study demonstrates the utility of a novel method to measure and assess results in the surgical revision of UCL/UCLP patients with secondary lip deformities. This knowledge can aid the surgeon in selection of treatment techniques.

Complete genome sequence of a novel recombinant avian leukosis virus isolated from a three-yellow chicken.

In this study, an avian leukosis virus (ALV) strain (GX-2020-01) was isolated from a three-yellow chicken, and its complete genome was 7570 bp long with the typical organization "5'LTR-gag-pol-env-3'LTR." Phylogenetic analysis and sequence comparison revealed that it belongs to the ALV-J subgroup. However, the LTR region of GX-2020-01 is highly similar to that of reference strains of ALV-K/E (96.61%-97.10%), demonstrating that this novel isolate is a natural recombinant. The replication efficiency of GX-2020-01 was significantly lower than the previously isolated ALV-J strain (NX0101), indicating that the recombination event might have resulted in slower virus replication, making it harder for it to be detected through routine testing.

The prevention and control of tuberculosis: an analysis based on a tuberculosis dynamic model derived from the cases of Americans.

BACKGROUND: Tuberculosis (TB), a preventable and curable disease, is claimed as the second largest number of fatalities, and there are 9,025 cases reported in the United States in 2018. Many researchers have done a lot of research and achieved remarkable results, but TB is still a severe problem for human beings. The study is a further exploration of the prevention and control of tuberculosis. METHODS: In the paper, we propose a new dynamic model to study the transmission dynamics of TB, and then use global differential evolution and local sequential quadratic programming (DESQP) optimization algorithm to estimate parameters of the model. Finally, we use Latin hypercube sampling (LHS) and partial rank correlation coefficients (PRCC) to analyze the influence of parameters on the basic reproduction number ([Formula: see text]) and the total infectious (including the diagnosed, undiagnosed and incomplete treatment infectious), respectively. RESULTS: According to the research, the basic reproduction number is computed as 2.3597 from 1984 to 2018, which means TB is also an epidemic in the US. The diagnosed rate is 0.6082, which means the undiagnosed will be diagnosed after 1.6442 years. The diagnosed will recover after an average of 1.9912 years. Moreover, some diagnosed will end the treatment after 1.7550 years for some reason. From the study, it's shown that 2.40% of the recovered will be reactivated, and 13.88% of the newborn will be vaccinated. However, the immune system will be lost after about 19.6078 years. CONCLUSION: Through the results of this study, we give some suggestions to help prevent and control the TB epidemic in the United States, such as prolonging the protection period of the vaccine by developing new and more effective vaccines to prevent TB; using the Chemoprophylaxis for incubation patients to prevent their conversion into active TB; raising people's awareness of the prevention and control of TB and treatment after illness; isolating the infected to reduce the spread of TB. According to the latest report in the announcement that came at the first WHO Global Ministerial Conference on Ending tuberculosis in the Sustainable Development Era, we predict that it is challenging to control TB by 2030.

Electrochemical assays for determination of H2O2 and prostate-specific antigen based on a nanocomposite consisting of CeO2 nanoparticle-decorated MnO2 nanospheres.

A nanocomposite consisting of CeO2 nanoparticle-decorated MnO2 nanospheres (CeO2@MnO2) was synthesized for the first time via a hydrothermal method. CeO2@MnO2 was exploited to construct an electrochemical assays for detecting H2O2 and prostate-specific antigen (PSA) with square wave voltammetry (SWV). The electrochemical results proved that CeO2@MnO2 owned a better electrocatalytic effect towards H2O2 reduction than pure MnO2 NS and CeO2 NP due to the synergistic effect between MnO2 NS and CeO2 NP. Under optimized conditions, CeO2@MnO2-based assay can be applied to detect H2O2 in the range 1 to 3.0 × 103 µmol L-1. The label-free electrochemical immunoassay based on CeO2@MnO2 displayed linearly with concentrations of PSA from 0.005 to 50.0 ng mL-1. The electrochemical assays also possessed acceptable sensitivity, selectivity, and stability. The study showed that CeO2@MnO2 hold great potential as a biosensing platform and the clinical determination of tumor markers in human serum. Graphical abstract A nanocomposite consisting of CeO2 nanoparticles decorated MnO2 nanospheres (CeO2 @MnO2) was firstly synthesized via a hydrothermal method. CeO2@MnO2 was firstly exploited to construct electrochemical assays for detecting H2O2 and prostate-specific antigen (PSA) with square wave voltammetry (SWV), respectively. The electrochemical results proved that CeO2@MnO2 owned better electrocatalysis towards H2O2 reduction than pure MnO2 NS and CeO2 NP due to the synergistic effect between MnO2 NS and CeO2 NP. Under optimized conditions, CeO2@MnO2 based assay relative to the H2O2 system can be applied to detect H2O2 with range from 1 to 3.0 × 103 µmol L-1. The label-free electrochemical immunoassay based on CeO2@MnO2 relative to the H2O2 system displayed linearly with concentrations of PSA from 0.005 to 50.0 ng mL-1. The electrochemical assays also possessed acceptable sensitivity, selectivity and stability. The study showed that CeO2@MnO2 hold great potential for biosensing platform and the clinic determination of tumor markers in human serum.

microRNA-124 attenuates isoflurane-induced neurological deficits in neonatal rats via binding to EGR1.

Isoflurane anesthesia induces neuroapoptosis in the development of the brain. In this study, neonatal rats and hippocampal neurons were subjected to isoflurane exposure, in which the effect of miR-124 on the neurological deficits induced by isoflurane was evaluated. Isoflurane anesthesia models were induced in neonatal SD rats aged 7 days and then treated with miR-124 agomir, miR-124 antagomir, or LV-CMV-early growth response 1 (EGR1) plasmids. Then, the spatial learning and memory ability of rats were evaluated by Morris water maze. Furthermore, primary hippocampal neurons cultured 7 days were also exposed to isoflurane and transfected with miR-124 agomir, miR-124 antagomir, or LV-CMV-EGR1 plasmids. The targeting relationship of miR-124 and EGR1 was verified by the dual-luciferase reporter gene assay. To identify the effect of miR-124 on neuron activities, the viability and apoptosis of hippocampal neurons were assessed. In response to isoflurane exposure, miR-124 expression was reduced and EGR1 expression was increased in the hippocampal tissues and neurons. The isoflurane anesthesia damaged rats' spatial learning and memory ability, and reduced viability, and promoted apoptosis of hippocampal neurons. EGR1 was targeted and negatively regulated by miR-124. The treatment of miR-124 agomir improved rats' spatial learning and memory ability and notably increased hippocampal neuron viability and resistance to apoptosis, corresponding to an increased brain-derived neurotrophic factor (BDNF) expression, inhibited expression of proapoptotic factors (cleaved-Caspase-3 and Bax), and enhanced the expression of antiapoptotic factor (Bcl-2). Upregulated miR-124 inhibited the expression of EGR1, by which mechanism miR-124 reduced the neurological deficits induced by isoflurane in neonatal rats through inhibiting apoptosis of hippocampal neurons.

KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients.

AIM: To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk. METHODS: The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTCKRT19, CTCCEACAM5 and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed. RESULTS: In different pathological stages of breast cancer, the rates of CTCKRT19-pos and CTCCEACAM5-pos increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTCKRT19-pos in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTCCEACAM5 and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047). CONCLUSION: Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.

Selective effect of cytokine-induced killer cells on survival of patients with early-stage melanoma.

Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months. Survival data and immune responses were evaluated after CIK cell treatment. In this study, CIK cells were successfully generated from peripheral blood of melanoma patients after in vitro culture for 14 days. The cultured CIK cells not only produced high levels of pro-inflammatory cytokines upon in vitro stimulation but also efficiently killed human melanoma cell lines. No serious side events were observed in all patients treated with CIK cells. Furthermore, infusions of CIK cells improved the quality of life in some patients, including advanced cases. More importantly, the CIK group exhibited better survival rates compared to the control group among early-stage melanoma patients, in consistent with the increased frequency of peripheral CD4+ T cells. However, the patients with advanced-stage melanoma did not benefit from the CIK cell therapy in terms of survival rate. In conclusion, CIK cells combined with conventional treatments may prolong the survival of early-stage melanoma patients and improve the quality of life for some advanced cases in a safe way.

Attenuating Hypoxia-Induced Apoptosis and Autophagy of Mesenchymal Stem Cells: the Potential of Sitagliptin in Stem Cell-Based Therapy.

BACKGROUND/AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleiotropic effects on cardiovascular protection beyond the antidiabetic property. However, it remains unknown that the impact of one DPP-4 inhibitor sitagliptin on the survival of mesenchymal stem cells (MSCs) in hypoxia and serum deprivation (H/SD) environment. METHODS: The apoptosis and autophagy of MSCs were analyzed in different concentrations of sitagliptin under H/SD condition. For later studies, we tested the relationship between anti-apoptotic and anti-autophagic effects of sitagliptin. The level of cell apoptosis was analyzed by Annexin V-FITC/PI staining, western blot of Bcl-2 and Bax proteins. Autophagy flux was assessed by multiple autophagy related proteins and substrates. Cell autophagy was identified by acridine orange staining, western blot of Beclin 1 and light chain 3 protein, and transmission electron microscopy. RESULTS: We demonstrated that sitagliptin attenuated hypoxia-induced apoptosis and autophagy of MSCs. Furthermore, sitagliptin regulated cell autophagy by Bcl-2/ Beclin 1 pathway in H/SD condition. CONCLUSIONS: This study provides insight into the utility of the DPP-4 inhibitor sitagliptin for MSCs transplantation in the ischemic microenvironment that extends its antidiabetic property.

Development and psychometric testing of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ) for postpartum depression.

This article describes the development and psychometric assessment of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ). There were four phases in this process: (1) the items were generated using a literature review and a focus group, (2) content validity was evaluated by an expert panel, (3) a pilot study was conducted with 45 postpartum women to refine the scale, and (4) a convenience sample of 256 postpartum women in China was recruited to complete the questionnaire. Construct validity was established by exploratory factor analysis; a four-factor structure of the scale was accepted (social and family, personality and relationship, mother and infant, maternal feelings and 'doing the month'). These factors explained 47.46 % of the variance. Pearson's correlation coefficient was conducted to test convergent validity with the Edinburgh Postnatal Depression Scale (EPDS) (r = 0.54; p < 0.001). The Cronbach's alpha coefficient of the four subscales ranged from 0.58 to 0.71. The final 18-item version of the questionnaire is potentially a valuable tool for assessing postnatal risk factors in Chinese postpartum mothers.

Predicting invasiveness of ground-glass nodules in lung adenocarcinoma: based on preoperative 18F-fluorodeoxyglucose PET/computed tomography and high-resolution computed tomography.

OBJECTIVE: This study was conducted to explore the differential diagnostic value of PET/computed tomography (PET/CT) combined with high-resolution computed tomography (HRCT) in predicting the invasiveness of ground-glass nodules (GGNs). MATERIALS AND METHODS: This retrospective analysis included 67 patients (mean age 62.5 ±â€…8.4, including 45 females and 22 males) with GGNs who underwent preoperative 18F-fluorodeoxyglucose (18F-FDG) PET/CT and HRCT examinations between January 2018 and October 2022. Based on the postoperative pathological results of lung adenocarcinoma, the patients were classified into two groups: invasive adenocarcinoma (IAC) and non-IAC. Besides, the clinical and imaging information of these patients was collected. HRCT signs include the existence of air bronchial signals, vascular convergence, pleural indentation, lobulation, and spiculation. Moreover, the diameter of solid components (DSolid), diameter of ground-glass nodules (DGGN), and computed tomography values of ground-glass nodules (CTGGN) were measured concurrently. Furthermore, the mean standardized uptake value, maximal standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis were assessed during PET/CT. Associations between invasiveness and these factors were evaluated using univariate and multivariate analyses. RESULTS: The results of logistic regression analysis demonstrated that DGGN, DSolid, consolidation tumor ratio (CTR), CTGGN, and SUVmax were independent predictors in the IAC group. The combined diagnosis based on these five predictors revealed that area under the curve was 0.825. CONCLUSION: The DGGN, DSolid, CTR, CTGGN, and SUVmax in GGNs were independent predictors of IAC, and combining 18F-FDG PET/CT metabolic parameters with HRCT may improve the predictive value of pathological classification in lung adenocarcinoma.

Evaluating the efficacy of mesenchymal stem cells for diabetic neuropathy: A systematic review and meta-analysis of preclinical studies.

Diabetic neuropathy affects nearly half of all diabetics and poses a significant threat to public health. Recent preclinical studies suggest that mesenchymal stem cells (MSCs) may represent a promising solution for the treatment of diabetic neuropathy. However, an objective assessment of the preclinical effectiveness of MSCs is still pending. We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane library to identify preclinical studies that investigate the effects of MSCs on diabetic neuropathy up until 15 September 2023. Outcome indicators consisted of motor and sensory nerve conduction velocities, intra-epidermal nerve fiber density, sciatic nerve blood flow, capillary-to-muscle fiber ratio, neurotrophic factors, angiogenic factors and inflammatory cytokines. The literature review and meta-analysis were conducted independently by two researchers. 23 studies that met the inclusion criteria were included in this system review for qualitative and quantitative analysis. Pooled analyses indicated that MSCs exhibited an evident benefit in diabetic neuropathy in terms of motor (SMD = 2.16, 95% CI: 1.71-2.61) and sensory nerve conduction velocities (SMD = 2.93, 95% CI: 1.78-4.07), intra-epidermal nerve fiber density (SMD = 3.17, 95% CI: 2.28-4.07), sciatic nerve blood flow (SMD = 2.02, 95% CI: 1.37-2.66), and capillary-to-muscle fiber ratio (SMD = 2.28, 95% CI: 1.55 to 3.01, p < 0.00001). Furthermore, after MSC therapy, the expressions of neurotrophic and angiogenic factors increased significantly in most studies, while the levels of inflammatory cytokines were significantly reduced. The relevance of this review relies on the fact that summarizes an extensive body of work entailing substantial preclinical evidence that supports the efficacy of MSCs in mitigating diabetic neuropathy. While MSCs emerge as a promising potential treatment for diabetic neuropathy, further research is essential to elucidate the underlying mechanisms and the best administration strategy for MSCs.

Extracellular Vesicles Derived from H2O2-Stimulated Adipose-Derived Stem Cells Alleviate Senescence in Diabetic Bone Marrow Mesenchymal Stem Cells and Restore Their Osteogenic Capacity.

Introduction: Autologous stem cell transplantation has emerged as a promising strategy for bone repair. However, the osteogenic potential of mesenchymal stem cells derived from diabetic patients is compromised, possibly due to hyperglycemia-induced senescence. The objective of this study was to assess the preconditioning effects of extracellular vesicles derived from H2O2-stimulated adipose-derived stem cells (ADSCs) and non-modified ADSCs on the osteogenic potential of diabetic bone marrow mesenchymal stem cells (BMSCs). Methods: Sprague-Dawley (SD) rats were experimentally induced into a diabetic state through a high-fat diet followed by an injection of streptozotocin, and diabetic BMSCs were collected from the bone marrow of these rats. Extracellular vesicles (EVs) were isolated from the conditioned media of ADSCs, with or without hydrogen peroxide (H2O2) preconditioning, using density gradient centrifugation. The effects of H2O2 preconditioning on the morphology, marker expression, and particle size of the EVs were analyzed. Furthermore, the impact of EV-pretreatment on the viability, survivability, migration ability, osteogenesis, cellular senescence, and oxidative stress of diabetic BMSCs was examined. Moreover, the expression of the Nrf2/HO-1 pathway was also assessed to explore the underlying mechanism. Additionally, we transplanted EV-pretreated BMSCs into calvarial defects in diabetic rats to assess their in vivo bone formation and anti-senescence capabilities. Results: Our study demonstrated that pretreatment with EVs from ADSCs significantly improved the viability, senescence, and osteogenic differentiation potential of diabetic BMSCs. Moreover, in-vitro experiments revealed that diabetic BMSCs treated with H2O2-activated EVs exhibited increased viability, reduced senescence, and enhanced osteogenic differentiation compared to those treated with non-modified EVs. Furthermore, when transplanted into rat bone defects, diabetic BMSCs treated with H2O2-activated EVs showed improved bone regeneration potential and enhanced anti-senescence function t compared to those treated with non-modified EVs. Both H2O2-activated EVs and non-modified EVs upregulated the expression of the Nrf2/HO-1 pathway in diabetic BMSCs, however, the promoting effect of H2O2-activated EVs was more pronounced than that of non-modified EVs. Conclusion: Extracellular vesicles derived from H2O2-preconditioned ADSCs mitigated senescence in diabetic BMSCs and enhanced their bone regenerative functions via the activation of the Nrf2/HO-1 pathway.

Efficacy of MSC-derived small extracellular vesicles in treating type II diabetic cutaneous wounds: a systematic review and meta-analysis of animal models.

Background: Small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have emerged as a promising therapy for treating type II diabetic cutaneous wounds. Currently, the evidence supporting the use of MSC-sEVs for treating diabetic skin wounds remains inconclusive and is limited to preclinical studies. To facilitate the clinical translation of cell-free therapy, conducting a comprehensive systematic review of preclinical studies assessing the efficacy of MSC-sEVs is imperative. Methods: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library databases until June 14, 2023, to identify studies that met our pre-established inclusion criteria. The outcome indicators comprised wound closure rate (primary outcome), neovascular density, re-epithelialization rate, collagen deposition, and inflammatory factors (secondary Outcomes). A fixed-effects model was employed in instances of low heterogeneity (I2<50%), while a random-effects model was utilized for high heterogeneity (I2≥50%). The risk of bias in animal studies was assessed using the SYRCLE tool. Results: Twenty-one studies were included in this meta-analysis. Compared with the control group, MSC-sEVs were found to significantly facilitate the healing of cutaneous wounds in type II diabetic patients (standardized mean difference [SMD]=3.16, 95% confidence interval [CI]: 2.65 to 3.66, P<0.00001, I2 = 39%). Conclusions: According to the meta-analysis of preclinical studies, MSC-sEVs show promising applications in promoting type II diabetic wound healing. As a result, translating these findings into clinical applications appears warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023375467.

One Fits Many: Class Confusion Loss for Versatile Domain Adaptation.

In the open world, various label sets and domain configurations give rise to a variety of Domain Adaptation (DA) setups, including closed-set, partial-set, open-set, and universal DA, as well as multi-source and multi-target DA. It is notable that existing DA methods are generally designed only for a specific setup, and may under-perform in setups they are not tailored to. This paper shifts the common paradigm of DA to Versatile Domain Adaptation (VDA), where one method can handle several different DA setups without any modification. Towards this goal, we first delve into a general inductive bias: class confusion, and then uncover that reducing such pairwise class confusion leads to significant transfer gains. With this insight, we propose one general class confusion loss (CC-Loss) to learn many setups. We estimate class confusion based only on classifier predictions and minimize the class confusion to enable accurate target predictions. Further, we improve the loss by enforcing the consistency of confusion matrices under different data augmentations to encourage its invariance to distribution perturbations. Experiments on 2D vision and 3D vision benchmarks show that the CC-Loss performs competitively in different mainstream DA setups.