Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge.

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

Novel integrated Omics based computational approach for drug repurposing for non-muscle invasive bladder cancer (NMIBC).

Non-muscle invasive bladder cancer (NMIBC) refers to a subtype of bladder carcinoma where cancer is localized in the inner lining of bladder. NMIBC consider as one of most costly malignancy and requires significant surgical and therapeutic measure. However, recurrence and progression of tumor is common in treated patients. Here we presented an integrated OMICs approach for the identification and inhibition of NMIBC specific genes. We utilized a case study where three group of patients were compared: 1) Relapsed tumors 2) recurrent tumors and 3) tumor in progression. Common transcriptome signature between patients facing recurrence and progression allowed us to identify three NMIBC specific genes FLT-1, WHSC-1 and CD34. We further utilized novel approach of Co-expressed gene-set enrichment analysis (COGENA) on the differentially expressed genes of this case study. Three drugs (paroxetine, adiphenine and H-89) with role of receptors inhibition were identified and predicted as repurposed drugs for the inhibition NMIBC specific genes. We further tested this hypothesis by performing molecular docking and simulation analysis between cancer specific proteins and drugs. FLT-1 have shown significant stable interaction with both drugs paroxetine and adiphenine whereas WHSC-1 have shown compact interaction with adiphenine and H-89. In the light of these evidence, we suggest that adiphenine could be repositioned as alternate targeted medicine for the treatment of NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug repurposing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.

Identification of potential phytochemical for the inhibition of non-muscle invasive bladder cancer (NMIBC).

Non-muscle invasive bladder cancer (NMIBC) is one of the most common type of bladder cancer. Here, we have utilized an integrated transcriptomic-computational approach to identify alternate treatments to the NMIBC. In this study, we have performed the comprehensive comparative analysis between three groups of 36 patients with non-relapsed (NR), recurrence and progressive symptoms. Differentially expressed genes involved in the pathways associated with the NMIBC were identified. In silico protein-protein interaction (PPI) network was performed to create the network of the hub genes associated with NMIBC. Further, we compared NR individuals with two cohorts of patients with recurrent and progressive symptoms that lead to the identification of three major biomarkers CD34, FLT1 and WHSC1 genes. Concurrently, PPI also suggests that they are significant hub genes responsible for disease recurrence and progression. Furthermore, targeted genes WHSC-1 and FLT-1 were subjected to virtual screening for identification phytochemical inhibitors. Docking and molecular dynamics simulations concluded that the phytochemicals anonymously named 'UNK' and '6-hydroxycyanidin' are suitable for the inhibition of the proteins causing the NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug designing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.

Nomogram for predicting the preoperative lymph node metastasis in resectable pancreatic cancer.

BACKGROUND: Lymph node metastasis (LNM) is a critical prognostic factor in resectable pancreatic cancer (PC) patients, determining treatment strategies. This study aimed to develop a clinical model to adequately and accurately predict the risk of LNM in PC patients. METHODS: 13,200 resectable PC patients were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database, and randomly divided into a training group and an internal validation group at a ratio of 7:3. An independent group (n = 62) obtained from The First Affiliated Hospital of Xinxiang Medical University was enrolled as the external validation group. The univariate and multivariate logistic regression analyses were used to screen independent risk factors for LNM. The minimum Akaike's information criterion (AIC) was performed to select the optimal model parameters and construct a nomogram for assessing the risk of LNM. The performance of the nomogram was assessed by the receiver operating characteristics (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, an online web calculator was designed to assess the risk of LNM. RESULT: A total of six risk predictors (including age at diagnosis, race, primary site, grade, histology, and T-stage) were identified and included in the nomogram. The areas under the curves (AUCs) [95% confidential interval (CI)] were 0.711 (95%CI: 0.700-0.722), 0.700 (95%CI: 0.683-0.717), and 0.845 (95%CI: 0.749-0.942) in the training, internal validation and external validation groups, respectively. The calibration curves showed satisfied consistency between nomogram-predicted LNM and actual observed LNM. The concordance indexes (C-indexes) in the training, internal, and external validation sets were 0.689, 0.686, and 0.752, respectively. The DCA curves of the nomogram demonstrated good clinical utility. CONCLUSION: We constructed a nomogram model for predicting LNM in pancreatic cancer patients, which may help oncologists and surgeons to choose more individualized clinical treatment strategies and make better clinical decisions.

Microwave ablation versus radiofrequency ablation for patients with primary and secondary hyperparathyroidism: a meta-analysis.

OBJECTIVE: Thermal ablation, including microwave ablation (MWA) and radiofrequency ablation (RFA), has been recommended for the treatment of primary hyperparathyroidism (PHPT) and refractory secondary hyperparathyroidism (SHPT). This meta-analysis was conducted to evaluate the efficacy and safety of MWA and RFA in patients with PHPT and refractory SHPT. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang were searched from inception to December 5, 2022. Eligible studies comparing MWA and RFA for PHPT and refractory SHPT were included. Data were analyzed using Review Manager software, version 5.3. RESULTS: Five studies were included in the meta-analysis. Two were retrospective cohort studies, and three were RCTs. Overall, 294 patients were included in the MWA group, and 194 patients were included in the RFA group. Compared with RFA for refractory SHPT, MWA had a shorter operation time for a single lesion (P < 0.01) and a higher complete ablation rate for a single lesion ≥ 15 mm (P < 0.01) but did not show a difference in the complete ablation rate for a single lesion < 15 mm (P > 0.05). There were no significant differences between MWA and RFA for refractory SHPT concerning parathyroid hormone (P > 0.05), calcium (P > 0.05), and phosphorus levels (P > 0.05) within 12 months after ablation, except that calcium (P < 0.01) and phosphorus levels (P = 0.02) in the RFA group were lower than those in the MWA group at one month after ablation. There was no significant difference between MWA and RFA concerning the cure rate of PHPT (P > 0.05). There were no significant differences between MWA and RFA for PHPT and refractory SHPT concerning the complications of hoarseness (P > 0.05) and hypocalcaemia (P > 0.05). CONCLUSION: MWA had a shorter operation time for single lesions and a higher complete ablation rate for large lesions in patients with refractory SHPT. However, there was no significant difference in efficacy and safety between MWA and RFA in cases of both PHPT and refractory SHPT. Both MWA and RFA are effective treatment methods for PHPT and refractory SHPT.

Association of Gut Microbiota Composition in Pregnant Women Colonized with Group B Streptococcus with Maternal Blood Routine and Neonatal Blood-Gas Analysis.

Group B Streptococcus (GBS) colonizes the vaginal and rectal mucosa in a substantial proportion of healthy women, and GBS is a risk factor for GBS-associated adverse birth outcomes, such as bacterial infection, in neonates. Whether changes in the gut microbiota of GBS-infected pregnant women are associated with maternal complete blood cell count (CBC) and neonatal blood-gas analysis is unknown. To explore the relationship between the intestinal microecological composition of pregnant women and maternal blood routine and neonatal blood-gas analysis, we collected intestinal microecology samples of 26 pregnant women in clinic. They were divided into a positive group(GBS positive,GBS +) and a negative group (GBS negative, GBS-), with 12 in the positive group and 14 in the negative group. 16S rRNA gene sequencing was used to examine the gut microbiota profile from a fecal sample of pregnant women. CBC was carried out in enrolled pregnant women and umbilical arterial blood-gas analysis (UABGA)was conducted for analysis of intestinal microbiota composition, maternal blood routine and neonatal blood gas. Our results showed significant differences in the total number of organisms and microbial diversity of intestinal microbiota between healthy pregnant women and GBS-positive pregnant women. Particularly, abundances of Lentisphaerae, Chlorobi, Parcubacteria, Chloroflexi, Gemmatimonadetes, Acidobacteria, Fusobacteria and Fibrobacteres were only detected in participants with GBS colonization. Blood-gas analysis revealed that neonates born to mothers with GBS colonization had significantly higher fractions of carboxyhemoglobin (FCOHb) and lower methemoglobin (FMetHb), and abundances of OTU80, OTU122, OTU518 and OTU375 were associated with blood-gas indicators, such as carboxyhemoglobin, methemoglobin, PCO2, PH and ABE. Interestingly, there were significant correlations between OTU levels and inflammatory indexes in pregnant women with GBS infection. Together, this study revealed for the first time that altered gut microbiota compositions are related to the inflammatory state in GBS-positive pregnant women and neonatal blood-gas indicators. GBS colonization may lead to significant changes in the gut microbiome, which might be involved in the pathogenesis of the maternal inflammatory state and neonatal blood gas abnormalities.

Aloe-emodin derivative produces anti-atherosclerosis effect by reinforcing AMBRA1-mediated endothelial autophagy.

Atherosclerosis is an inflammatory disease of high lethality associated with endothelial dysfunction. Due to the pathophysiological complexity and our incomplete understanding of the mechanisms for the development and progression of atherosclerosis, effective means for the prevention and treatment of atherosclerosis still need further exploration. This study was designed to investigate the potential effects and underlying mechanisms of aloe-emodin derivative (AED) on atherosclerosis. High fat diet (HFD) treated ApoE-/- mice were used as an animal model of atherosclerosis. Intragastric administration of aloe-emodin (AE) or AED for 12 weeks markedly reduced the atherosclerotic plaque in aorta with decreased plaque area, lipid accumulation, macrophage infiltration, collagen content and metabolic abnormalities. By comparison, AED produced more potent anti-atherosclerosis effects than AE at the same dose. AED enhanced production of autophagy flux in cultured human aortic endothelial cells (HAECs). Moreover, AED increased the expression of activating molecule in Beclin1-regulated autophagy 1 (AMBRA1), a key protein involved in autophagosome formation. Furthermore, knockdown of AMBRA1 blocked the promotion effect of AED on autophagy in HAECs. Taken together, AED facilitates endothelial autophagy via AMBRA1 during the progression of atherosclerosis, suggesting the potential application of this compound for atherosclerosis treatment.

Factor Analysis and Psychometric Properties Adaption of Chinese Version of the Decisional Engagement Scale (DES-10).

OBJECTIVE: To translate and validate the DES-10 into Chinese and adapt the DES-10 among Chinese prostate cancer patients. To explore the impact of demographic data on the SDM of Chinese prostate cancer patients. METHODS: Data were collected from December 2019 to January 2020 from four hospitals among prostatic cancer patients in Henan Province, by convenience sampling method. A demographic questionnaire, DES-10, and 9-item Shared Decision Making Questionnaire (SDM-Q-9) were administered. The exploratory and confirmatory factor analysis was carried out to test the content, construct, reliability, and concurrent validity of the translated DES-10. Then, Pearson's correlation, t-test, and analysis of variance were used to test the demographic difference of DES-10. RESULTS: A total of 380 prostatic cancer patients completed the survey (96% response rate). The total score of DES-10 was 71.16±17.14. The Cronbach's ɑ coefficient was 0.87. Single factor structure was confirmed by exploratory factor analysis (explaining 50.14% of the variance). Model fitting indexes (RMSEA=0.07, CMIN/DF=2.92) were acceptable. The DES-10 scale showed good validity with the SDM-Q-9 as the criterion. Age, marital status, homeplace, and household monthly income could affect the shared decision-making of prostatic cancer patients. CONCLUSION: The DES-10 was demonstrated to be a valid and reliable scale to assess the prostatic cancer patient's engagement in health care decision-making. And it is culturally appropriate for use in China. The influence of age, marital status, homeplace, and household monthly income should be considered in promoting patients' participation in shared decision-making.

NK cell-derived exosomes improved lung injury in mouse model of Pseudomonas aeruginosa lung infection.

BACKGROUND: Pseudomonas aeruginosa (PA) is one of the most common bacteria that causes lung infection in hospital. The aim of our study is to explore the role and action mechanism of NK cells in lung PA infection. METHODS: In this present study, 2.5 × 108 CFU/mouse PA was injected into murine trachea to make lung PA infection mouse model. Anti-asialo GM1 was used to inhibit NK cell. The percentage of NK cells was ensured by flow cytometry, and the M1- and M2-polarized macrophages were determined by flow cytometry, qRT-PCR, and ELISA assay. Besides, H&E staining was performed to ensure the pathological changes in lung tissues. Transmission electron microscopy and western blot were carried out to identify the exosome. RESULTS: Here, in the mouse model of PA lung infection, NK cell depletion caused M2 polarization of lung macrophage, and exacerbated PA-induced lung injury. Next, our data shown that M2 macrophage polarization was enhanced when the generation of NK cell-derived exosome was blocked in the co-culture system of NK cells and macrophages. Subsequently, we demonstrated that NK cells promoted M1 macrophage polarization both in PA-infected macrophage and the mouse model of PA lung infection, and attenuated lung injury through exosome. CONCLUSION: Overall, our data proved that NK cell may improve PA-induced lung injury through promoting M1 lung macrophage polarization by secreting exosome. Our results provide a new idea for the treatment of PA lung infection.

Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3.

Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction (TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II (AngII). Emodin upregulated expression of metastasis associated protein 3 (MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis; in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis via upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.

E4BP4 facilitates glucocorticoid sensitivity of human bronchial epithelial cells via down-regulation of glucocorticoid receptor-beta.

It has recently been recognized that a subset of asthma patients suffer from glucocorticoid (GC) insensitivity, and glucocorticoid receptor-ß (GR-ß) is associated with corticosteroid resistance, but the underlying mechanisms remain unknown. Here we demonstrated that Interleukin-17A induced glucocorticoid sensitivity in human bronchial epithelial cells (16HBE) is enhanced, which is depend on E4 promoter-binding protein 4 (E4BP4) mediated GR-ß expression. Our data show that the expression of E4BP4 is significantly up-regulated in 16HBE cells, and the depletion of E4BP4 dramatically decreased glucocorticoid sensitivity in IL-17A induced 16HBE cells. Mechanistic studies revealed that E4BP4 plays a crucial role in Interleukin-17A induced glucocorticoid sensitivity in 16HBE cells via down-regulating GR-ß, which is probably mediated by PI3K/Akt activation. Collectively, we can draw the conclusion that E4BP4 contribute to enhance the GCs sensitivity, which may offer a new strategy for therapeutic intervention for GC-insensitive asthma.

Iridoids with Genipin Stem Nucleus Inhibit Lipopolysaccharide-Induced Inflammation and Oxidative Stress by Blocking the NF-κB Pathway in Polycystic Ovary Syndrome.

BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, and it is usually characterized by chronic inflammation, oxidative stress, and altered microRNA expression. The aim of this study is to investigate how the effects of iridoids with genipin stem nucleus inhibit PCOS complications. The interactions between iridoids were investigated, as well. METHODS: The chronic inflammation cell model was induced using lipopolysaccharide (LPS) in the RAW 264.7 and KGN cell lines. Levels of mRNA and protein expression were quantified using real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The target of the iridoids was identified using the drug affinity responsive target stability (DARTS) method. The ability to scavenge free radicals was evaluated using the DPPH radical scavenging method and the ultra oxygen anion (O2-) radical scavenging method. RESULTS: The cells recovered from the inflammatory conditions and showed significantly decreased levels of interleukins after treatment with iridoids. The iridoids were demonstrated to target NF-κB, inhibit the phosphorylation and degradation of IκB, inhibit the nuclear entry of NF-κB, and inhibit the expression of inflammatory factors. Though only genipin showed an efficient ability to scavenge O2-, the iridoids, IκB inhibitor (BAY 11-7085), and NF-κB inhibitor (PDTC) could inhibit LPS-induced oxidative stress on the cells, indicating that the iridoids exert their anti-oxidant effects via the NF-κB pathway. The expression levels of microRNAs (miRNAs) were also altered by LPS, but the iridoids could scarcely rescue the abnormal condition. CONCLUSION: Chronic inflammation may be an important incentive for oxidative stress and abnormal microRNA expression in PCOS, and iridoids can protect patients from inflammatory damage by regulating the NF-κB pathway.

Vaccination with DKK1-derived peptides promotes bone formation and bone mass in an aged mouse osteoporosis model.

The investigation of agents for the treatment of osteoporosis has been a long-standing effort. The Wnt pathway plays an important role in bone formation and regeneration, and expression of Wnt pathway inhibitors, Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of DKK1 leads to substantially increased bone mass in genetically manipulated animals. DKK1-derived peptides (DDPs) were added to BMP2-stimulated MC3T3-E1 preosteoblastic cells in vitro to evaluate inhibitory activity of DDPs in MC3T3-E1 cell differentiation. Study was extended in vivo on old female mice to show whether or not inhibition of endogenous DKK1 biological activity using DDPs vaccination approach leads to increase of bone formation, bone density, and improvement of bone microstructure. We reported that synthetic DDPs were able to reduce alkaline phosphatase activity, prevent mineralization and inhibit the differentiation of MC3T3-E1 cells in vitro. Furthermore, vaccination with these DDPs in aged female mice 4 times for a total period of 22 weeks promoted bone mass and bone microstructure. 3D microCT and histomorphometric analysis showed that there were significant increase in bone mineral densities, improvement of bone microstructure and promotion of bone formation in the vaccinated mice, especially in the mice vaccinated with DDP-A and DDP-C. Histological and scanning electron microscopy image analysis also indicated that vaccination increased trabecular bone mass and significantly decreased fragmentation of bone fibers. Taken together, these preclinical results suggest that vaccination with DDPs represents a promising new therapeutic approach for the treatment of bone-related disorders, such as osteoporosis.

Praziquantel derivatives with antischistosomal activity: aromatic ring modification.

A series of aromatic ring-modified praziquantel derivatives were prepared and evaluated against juvenile and adult stage of Schistosoma japonicumin. Several analogs comparable in activity to the drug praziquantel have been identified based on in vitro and in vivo japonuicum schistosomes worm viability assay. Structure and activity relationship of these praziquantel aromatic ring-modified compounds was revealed. Specifically, a compound in which a bromine has been introduced in the aromatic ring of praziquantel demonstrated close antischistosomal activity to praziquantel in vivo.