Evaluation of image-pro plus assisted superb microvascular imaging for differential diagnosis of renal masses.

OBJECTIVE: Previous research on diagnostic assessment by superb microvascular imaging (SMI) were based on qualitative or semi-quantitative assessments of vascularity, which may be subjective and unrepeatable by different sonographers. This study aimed to evaluate diagnostic performance of SMI Image-pro Plus (IPP) based vascular index (VI) for malignant renal masses. METHOD: We retrospectively reviewed 222 masses in 214 patients who underwent SMI between August 2019 and August 2022 in our study. We evaluated the diagnostic performance of blood flow via Alder grade, VI based on both IPP and SMI. RESULTS: The kappa consistency of the Adler grade and VI for renal masses was classified among different observers were 0.765 and 0.824. The intra-observers correlation ecoefficiency (ICC) were 0.727 and 0.874. Benign renal masses were mainly Adler grade 0, grade I, and grade II, VI was 4.30 ± 4.27 (Range 0.98-16.42); while malignant masses were mainly Adler grade III, VI was 14.95 ± 10.94 (Range 0.79-56.89). VI was higher in malignant than benign masses (t = 15.638, P < 0.01). Among the malignant masses, the mean VI in clear cell renal cell carcinoma was higher than that in papillary renal cell carcinoma and chromophobe renal cell carcinoma (F = 30.659, P < 0.01). The sensitivity, specificity and accuracy of SMI were 80.00%, 71.15%, and 78.64%, respectively. The sensitivity, specificity, and accuracy were 60.59%, 88.46%, and 80.18% by using a VI of 7.95 as the cutoff value to identify malignant lesions from benign masses yielded. VI had better diagnostic efficiency than ultrasonic characteristics and Adler grade in benign and malignant differential diagnosis (Z = 4.851, P < 0.01; Z = 2.732, P < 0.01). CONCLUSION: VI was higher in malignant than benign in renal masses. In malignant masses, VI in CCRCC was higher than that in papillary renal cell carcinoma and ChRCC. As a noninvasive examination, it had important clinical significance in the differential diagnosis of renal masses. VI from IPP may assist sonographer in distinguish renal malignances as a quantitative tool for vascularity.

Microbacterium salsuginis sp. nov., a halotolerant actinobacterium with antimicrobial activity.

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).

Arbuscular mycorrhizal fungi improve the competitive advantage of a native plant relative to a congeneric invasive plant in growth and nutrition.

Plant invasions severely threaten natural ecosystems, and invasive plants often outcompete native plants across various ecosystems. Arbuscular mycorrhizal (AM) fungi, serving as beneficial microorganisms for host plants, can greatly influence the competitive outcomes of invasive plants against native plants. However, it remains unclear how AM fungi alter the competitive balance between native and invasive species. A competitive experiment was conducted using an invasive Eupatorium adenophorum paired with a native congener Eupatorium lindleyanum. Specifically, both species were inoculated with (M+) or without (M-) the fungus Glomus etunicatum under intraspecific (Intra-) and interspecific (Inter-) competition. Plant traits were measured and analyzed regarding the growth and nutrition of both species. The results exhibited that the AM fungus significantly increased the height, diameter, biomass, C, N, and P acquisition of both the invasive E. adenophorum and the native E. lindleyanum. The root mycorrhizal colonization and the mycorrhizal dependency of native E. lindleyanum were greater than those of invasive E. adenophorum. Under M+, the Inter-competition inhibited the growth and nutrition of invasive E. adenophorum compared to the Intra- competition. Further, native E. lindleyanum exhibited higher competitiveness than invasive E. adenophorum in growth and nutrition. Meanwhile, the AM fungus significantly improved the competitiveness of native E. lindleyanum over invasive E. adenophorum. In conclusion, AM fungus improved the competitive advantage of native E. lindleyanum over invasive E. adenophorum in growth and nutrition, potentially contributing to native species competitively resisting the invasion of exotic species. These findings emphasize the importance of AM fungi in helping native plants resist the invasion of exotic plants and further contribute to understanding plant invasion prevention mechanisms.

Construction of an EMT-related lncRNA prognostic signature for lung adenocarcinoma and functional verification of its hub gene LINC01615.

BACKGROUND: The epithelial-mesenchymal transition (EMT) plays a vital role in the progression of lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) participate in the EMT process as an important regulatory factor and have the potential to serve as prognostic biomarkers. We aimed to construct a novel lncRNA prognostic signature for LUAD based on EMT-related lncRNAs, identify EMT-related hub lncRNA, and investigate its biological functions. METHODS: RNA-seq data, clinical and survival information were obtained from The Cancer Genome Atlas database. The EMT-related lncRNA prognostic signature (EMTscore) was constructed using the Least Absolute Shrinkage and Selection Operator Cox regression analysis. The efficiency of EMTscore in predicting the prognosis of LUAD was evaluated through the area under the time-dependent receiver operating characteristic (ROC) curves. The hub lncRNA of the prognostic signature was selected using a co-expression network map, and its effects on cell proliferation and metastasis were explored by in vitro experiments. RESULTS: We constructed a prognostic signature (EMTscore) containing 8 tumor-high expressed lncRNAs. The EMTscore performed well in predicting overall survival rates with AUC values of 0.708 at 5 years in the training set. EMTscore could independently predict the survival of LUAD, with HR = 4.011 (95% CI 2.430-6.622) in the multivariate Cox regression. Importantly, we identified LINC01615 as the hub lncRNA in the EMTscore and revealed that LINC01615 enhanced the proliferation, migration, and EMT of lung cancer cells. CONCLUSIONS: A new EMT-related lncRNA prognostic signature named EMTscore was developed, and LINC01615 was identified as the hub lncRNA of EMTscore. The hub lncRNA LINC01615 had an oncogenic biological function in LUAD.

The nucleolar protein NIFK accelerates the progression of colorectal cancer via activating MYC pathway.

This study aimed to explore the function of nucleolar protein interacting with the FHA domain of MKI67 (NIFK) on colorectal cancer (CRC) and its associated molecular mechanisms. NIFK was upregulated in CRC tissues and cells. NIFK silencing resulted in reduced cell growth and metastasis, as well as in promoted apoptosis in CRC cells. Moreover, NIFK silencing was also confirmed to inhibit lipid accumulation and decrease fatty acid synthesis via downregulating lipogenic enzymes in CRC cells. Gene set enrichment analysis and western blot co-verified that NIFK silencing inhibited MYC proto-oncogene, bHLH transcription factor (MYC) pathway in CRC cells. In addition, we also revealed that NIFK silencing function on cell growth, apoptosis, metastasis, and fatty acid metabolism in CRC might be cancelled after c-MYC overexpression. Silencing NIFK could inhibit cell growth and metastasis, and promoted apoptosis, as well as regulated fatty acid metabolism by inhibiting MYC pathway in CRC.

The Mechanisms of Resistin-Like Molecule-ß-Mediated Airway Inflammation in Chronic Obstructive Pulmonary Disease via Autophagy.

Background: The role of irreversible airway inflammatory damage in chronic obstructive pulmonary disease (COPD) progression is evident. Autophagy is an essential process in the cellular material metabolic cycle, and a family of resistant vegetative molecules may be involved in the COPD autophagic process. In this study, we investigated the mechanism of resistin-like molecule ß (RELMß) in COPD smoking-induced autophagy. Methods: Firstly, the expression differences of RELMß and autophagy markers between COPD and control groups were analyzed in the Gene Expression Omnibus (GEO) datasets and clinical specimens. Secondly, in vitro and in vivo experiments were conducted using immunoblotting, immunofluorescence, immunohistochemistry, and other methods to investigate the mechanism by which RELMß promotes airway inflammation through autophagy in a cigarette smoke extract-induced 16HBE cell inflammation model and a cigarette smoke-induced COPD-like mouse model. In addition, immunoprecipitation was used to analyze the binding of RELMß to the membrane protein TLR4. Results: The expression of RELMß and autophagy genes p62 and LC3B in lung tissue of COPD patients was significantly increased. RELMß can mediate the activation of autophagy in 16HBE cells, and through autophagy, it increases the expression of inflammatory cytokines in a cigarette smoke extract-induced 16HBE cell inflammation model. RELMß promotes cigarette smoke-induced COPD-like mouse airway inflammation through autophagy, and RELMß can mediate signal transduction through the cell membrane receptor TLR4. Conclusion: The RELMß binds to TLR4 to encourage signal transduction and that RELMß can promote inflammation in smoky COPD lungs through autophagy.

Elevated estradiol levels on hCG trigger day adversely effects on the clinical pregnancy rates of blastocyst embryo transfer but not cleavage-stage embryo transfer in fresh cycles: a retrospective cohort study.

Background: Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. Methods: This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001-3,000 pg/ml), set 3 (E2 = 3,001-4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. Results: The multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72-0.96], P = 0.012). Conclusions: Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.

Comparison of Three Ovulation Induction Therapies for Patients With Polycystic Ovary Syndrome and Infertility.

The purpose of this research was to evaluate the efficacy of 3 ovulation induction therapies for treating infertility in patients with polycystic ovary syndrome (PCOS). In this retrospective study, we compared the success rates of 90 patients who underwent intrauterine insemination, who were randomly assigned to 1 of 3 treatment groups: letrozole (LE) + urinary gonadotropin (human menopausal gonadotropin [HMG]), clomiphene (CC) + HMG, or HMG alone. Using ultrasound scanning, we examined the number of mature follicles, ovulation rate, clinical pregnancy rate, endometrial thickness, and blood flow. When compared to the other 2 groups, the LE + HMG group had significantly higher levels of mature follicles, ovulation rate, clinical pregnancy rate, estradiol, and luteinizing hormone on the day of the human chorionic gonadotropin injection and endometrial receptivity (P < .05). There was no statistically significant difference between the 3 groups in terms of abortion rate, ectopic pregnancy rate, or adverse reactions. In this research, we found that infertility in patients with PCOS could be effectively treated by combining LE with HMG. This protocol increased ovulation, boosted fertility, and enhanced endometrial receptivity with no increase in adverse reactions. Therefore, it may be a useful clinical approach for inducing ovulation and treating infertility in patients with PCOS.

Invasive and Native Plants Differentially Respond to Exogenous Phosphorus Addition in Root Growth and Nutrition Regulated by Arbuscular Mycorrhizal Fungi.

Plant invasion has severely damaged ecosystem stability and species diversity worldwide. The cooperation between arbuscular mycorrhizal fungi (AMF) and plant roots is often affected by changes in the external environment. Exogenous phosphorus (P) addition can alter the root absorption of soil resources, thus regulating the root growth and development of exotic and native plants. However, it remains unclear how exogenous P addition regulates the root growth and development of exotic and native plants mediated by AMF, affecting the exotic plant invasion. In this experiment, the invasive plant Eupatorium adenophorum and native plant Eupatorium lindleyanum were selected and cultured under intraspecific (Intra-) competition and interspecific (Inter-) competition conditions, involving inoculation with (M+) and without AMF (M-) and three different levels of P addition including no addition (P0), addition with 15 mg P kg-1 soil (P15), and addition with 25 mg P kg-1 soil (P25) for the two species. Root traits of the two species were analyzed to study the response of the two species' roots to AMF inoculation and P addition. The results showed that AMF significantly promoted the root biomass, length, surface area, volume, tips, branching points, and carbon (C), nitrogen (N), and P accumulation of the two species. Under M+ treatment, the Inter- competition decreased the root growth and nutrient accumulation of invasive E. adenophorum but increased the root growth and nutrient accumulation of native E. lindleyanum relative to the Intra- competition. Meanwhile, the exotic and native plants responded differently to P addition, exhibiting root growth and nutrient accumulation of invasive E. adenophorum increased with P addition, whereas native E. lindleyanum reduced with P addition. Further, the root growth and nutrition accumulation of native E. lindleyanum were higher than invasive E. adenophorum under Inter- competition. In conclusion, exogenous P addition promoted the invasive plant but reduced the native plant in root growth and nutrient accumulation regulated by AMF, although the native plant outcompeted the invasive plant when the two species competed. The findings provide a critical perspective that the anthropogenic P fertilizer addition might potentially contribute to the successful invasion of exotic plants.

Non-coding RNAs and colitis-associated cancer: Mechanisms and clinical applications.

BACKGROUND: Colitis-associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non-coding RNAs are closely involved and play a key role. METHODS: This review aims to summarise the major findings of non-coding RNAs in the development of CAC and present the potential mechanistic links between non-coding RNAs and CAC pathogenesis. The results show that non-coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non-coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non-coding RNAs. Besides, non-coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), Toll-like receptor 4 (TLR4), Wnt/ß-catenin and phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non-coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. CONCLUSIONS: It is believed that a deepening understanding of non-coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.

Advances in the role of STAT3 in macrophage polarization.

The physiological processes of cell growth, proliferation, differentiation, and apoptosis are closely related to STAT3, and it has been demonstrated that aberrant STAT3 expression has an impact on the onset and progression of a number of inflammatory immunological disorders, fibrotic diseases, and malignancies. In order to produce the necessary biological effects, macrophages (M0) can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) types in response to various microenvironmental stimuli. STAT3 signaling is involved in macrophage polarization, and the research of the effect of STAT3 on macrophage polarization has gained attention in recent years. In order to provide references for the treatment and investigation of disorders related to macrophage polarization, this review compiles the pertinent signaling pathways associated with STAT3 and macrophage polarization from many fundamental studies.

A new B cell epitope of pC129R protein of African swine fever virus identified by monoclonal antibodies.

African swine fever virus (ASFV) is a most important pathogen which causes huge damage in swine production in the world. pC129R protein is one of the most abundant ASFV proteins in infected Vero cells and WSL-HP cells, which consequently could be a target for ASF detection and surveillance. In this study, 5-6-week-old female BALB/c mice were immunized with rpC129R protein expressed by a prokaryotic system. And three hybridomas, 1B1, 1B4 and 4H4, steadily secreted anti-pC129R monoclonal antibodies were screened by an indirect enzyme linked immunosorbent assay (ELISA). Among them, 1B4 and 4H4 had IgG2a isotype with Kappa light chain, while 1B1 had IgG1 isotype with Kappa light chain. Western blot and indirect immunofluorescence assay showed that three monoclonal antibodies (mAbs) specifically reacted with ASFV. Epitope mapping was performed with truncated polypeptides. And a new B cell epitope, 18KHYVLIPK25 was identified by the mAbs, which was highly conserved in most genotypes of ASFV. These findings not only provide a monoclonal antibody tool for further study of the function of C129R, but also lay the foundation for serological diagnosis and vaccine development.

Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer.

Introduction: The diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings. Methods: The plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland). Results: The positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42. Discussion: In conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.

Association between the methylation of CpG islands in JAK-STAT pathway-related genes and colorectal cancer.

BACKGROUND: Aberrant promoter methylation of CpG islands plays an important role in carcinogenesis. However, the association between the DNA methylation of JAK-STAT pathway-related genes in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility remains unclear. METHODS: We conducted a case-control study of 403 patients with CRC and 419 cancer free controls, and the DNA methylation levels of JAK2, STAT1, STAT3, and SOCS3 in peripheral blood samples from all subjects were assessed using a methylation-sensitive high-resolution melting (MS-HRM) analysis. RESULTS: Compared with controls, the methylation of the JAK2, STAT1 and SOCS3 genes increased the CRC risk (ORadjusted=1.96, 95% CI, 1.12-3.41, P=0.01; ORadjusted=5.37, 95% CI, 3.74-7.71, P<0.01; ORadjusted=3.30, 95% CI, 1.58-6.87, P<0.01). In the multiple CpG site methylation (MCSM) analysis, a high MCSM value denoted an increased CRC risk (ORadjusted=4.97, 95% CI, 3.34-7.37, P<0.01). CONCLUSION: In peripheral blood, the methylation of JAK2, STAT1, and high levels of MCSM are promising biomarkers for CRC risk.

Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

Gardenoside ameliorates inflammation and inhibits ECM degradation in IL-1ß-treated rat chondrocytes via suppressing NF-κB signaling pathways.

Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment beside late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Gardenoside is a naturally compound extracted from Gardenia jasminoides Ellis, which has a variety of anti-inflammatory effects. However, few studies have been conducted to determine the role of gardenoside in OA. This study aimed to explore whether gardenoside has effect in OA treatment. Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of gardenoside at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Via in vitro experiments, our study found that gardenoside lowers the gene expression of COX-2, iNOS, IL-6, and reduced the ROS production of chondrocytes induced by IL-1ß. Moreover, it effectively alleviates ECM degradation caused by IL-1ß and promotes the ECM synthesis in chondrocytes by upregulating collagen-II and the ACAN expression, downregulating the expression of MMP-3, MMP-13, and ADAMTS-5 expression. Further, our study showed that gardenoside inhibits NF-κB signaling pathway activated by IL-1ß in chondrocytes. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with gardenoside into the knee articular cavity. In vivo study suggested that gardenoside attenuates OA progression in rats. As a whole, in vitro and in vivo results highlight gardenoside is a promising OA treatment agent.

Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm.

Melanocyte damage, innate immune response, adaptive immune response, and immune inflammatory microenvironment disorders are involved in the development of the immunological pathogenic mechanism of vitiligo. Mesenchymal stem cells are considered an ideal type of cells for the treatment of vitiligo owing to their low immunogenicity, lower rates of transplant rejection, and ability to secrete numerous growth factors, exosomes, and cytokines in vivo. The regulation of signaling pathways related to oxidative stress and immune imbalance in the immunological pathogenesis of vitiligo can improve the immune microenvironment of tissue injury sites. In addition, co-transplantation with melanocytes can reverse the progression of vitiligo. Therefore, continuous in-depth research on the immunopathogenic mechanism involved in this disease and mesenchymal stem cell-based therapy is warranted for the treatment of vitiligo in the future.

A Study on the Prediction of Reproductive Outcomes in Frozen Embryo Transfer Cycles by Calculating the Volume of Uterine Junctional Zone with Three-Dimensional Ultrasound.

PURPOSE: To prospectively study the influence of the volume of the uterine junctional zone (JZ) as a novel predictor of reproductive outcomes in frozen embryo transfer cycles. METHODS: Among the first 30 patients, intra- and interobserver repeatability was evaluated and expressed as a coefficient of repeatability. The same classification system was used to evaluate the JZ of 142 infertility patients undergoing in vitro fertilization (IVF). Ultrasonography was performed on the day before transplantation. The three-dimensional (3D) volume images were then analyzed to obtain the volume of the endometrium (EV), the average thickness of the JZ on the coronal plane, and the volume of the JZ (JZV). The JZV was then divided by the EV. These parameters were compared with the outcomes of clinical pregnancy. RESULTS: The 3D image showed that the JZ achieved a good intra- and interobserver consistency (k = 0.862, k = 0.694). The total pregnancy rate was 47%. There was a highly significant difference between pregnant and non-pregnant women with respect to age (p < 0.001), JZV (p = 0.003), and JZV/EV (p < 0.001) on the day before transplantation. Age and JZV/EV were independent factors for predicting the success of IVF transplantation (p = 0.010, p = 0.016). The area under the ROC curve of JZV/EV in predicting clinical pregnancy was 0.688, the cut-off value was 0.54, the sensitivity was 83.8%, and the specificity was 50.0%. CONCLUSION: Age and JZV/EV are independent factors for predicting the success of frozen embryo transfer cycles in IVF. A smaller JZV/EV was more beneficial for clinical pregnancy.

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study.

Purpose: Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods: Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results: We found that MA could down-regulate the IL-1ß-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1ß. Moreover, MA protects chondrocytes from IL-1ß-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1ß-induced chondrocytes. Conclusion: These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

Identification of the key genes in chronic obstructive pulmonary disease by weighted gene co-expression network analysis.

Background: Chronic obstructive pulmonary disease (COPD) is prevalent mainly in older adults, especially those who are smokers. It appears to be regulated by multiple genes, but there is some degree of familial clustering. The evidence to date suggests that COPD-associated biomarkers are largely inadequate for disease diagnosis, so we conducted a comprehensive search for more specific genetic markers. Methods: We used 3 datasets from the Gene Expression Omnibus (GEO) database. By investigating the biological information [i.e., Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and weighted gene co-expression network analysis (WGCNA)], we filtered out 8 differentially expressed genes (DEGs) and validated the transcript levels of those hub genes in 16HBE cell lines, THP-1 cell lines and lung tissue of COPD patients. Results: The 8 hub genes comprised amyloid precursor protein (APP), fibronectin 1, insulin-like growth factor 1 (IGF1), ß-actin, capping actin protein of muscle Z-line subunit alpha 2, secreted phosphoprotein 1 (SPP1), catalase (CAT), and colony stimulating factor 2 (CSF2) were selected from among the DEGs. Cigarette smoke extract-stimulated 16HBE cells were found to highly express SPP1, CSF2, and IGF1. In addition, IGF1 levels were increased and IGF1 and APP levels were decreased in CSE-stimulated THP-1 cells. SPP1 and FN1 showed increased expression levels in lung tissue of COPD patients, but the opposite held for APP and CAT. Conclusions: We identified 8 hub genes of COPD based on GO, KEGG and WGCNA, which have provided insights into the pathophysiological mechanisms of COPD.