High-fat-diet-induced obesity promotes simultaneous progression of lung cancer and atherosclerosis in apolipoprotein E-knockout mice.

Background: Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE-/-) mice. Methods: Male ApoE-/- mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured. Results: At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204). Conclusions: In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

High fat diet increases the severity of collagen-induced arthritis in mice by altering the gut microbial community.

OBJECTIVES: Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice. METHODS: Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA. RESULTS: HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance of Blautia, Oscillibacter, Ruminiclostridium-9, and Lachnospiraceae UCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels. CONCLUSIONS: This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice.

BACKGROUND: Atherosclerosis (AS), a chronic inflammatory disease of blood vessels, is a major contributor to cardiovascular disease. Dental pulp stem cells (DPSCs) are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflammation-related diseases. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases. AIM: To modify DPSCs with HGF (DPSC-HGF) and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout (ApoE-/-) mouse model and an in vitro cellular model. METHODS: ApoE-/- mice were fed with a high-fat diet (HFD) for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs (DPSC-Null) through tail vein at weeks 4, 7, and 11, respectively, and the therapeutic efficacy and mechanisms were analyzed by histopathology, flow cytometry, lipid and glucose measurements, real-time reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay at the different time points of the experiment. An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells (HAOECs), and indirect co-cultured with supernatant of DPSC-Null (DPSC-Null-CM) or DPSC-HGF-CM, and the effect and mechanisms were analyzed by flow cytometry, RT-PCR and western blot. Nuclear factor-κB (NF-κB) activators and inhibitors were also used to validate the related signaling pathways. RESULTS: DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors, and the percentage of macrophages in the aorta, and DPSC-HGF treatment had more pronounced effects. DPSCs treatment had no effect on serum lipoprotein levels. The FACS results showed that DPSCs treatment reduced the percentages of monocytes, neutrophils, and M1 macrophages in the peripheral blood and spleen. DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-α stimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway. CONCLUSION: This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/- mice on a HFD, and could be of greater value in stem cell-based treatments for AS.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Co-overexpression of OPN, IGF-1 and CNTF augment the therapeutic effect of DPSC on spinal cord injury.

Background aims: Spinal cord injury (SCI) is one of the most complex and destructive diseases of the nervous system, which can lead to permanent loss of tactile perception. But existing treatment methods have limited effects. To establish a novel method that may be therapeutic in repairing the injured spinal cord, gene-modified dental pulp stem cells (DPSCs) were injected in situ. Methods: Adenovirus carrying osteopontin (OPN), Insulin-like growth factor 1 (IGF-1) and cailiary-derived neurotrophic factor (CNTF) (Ad-OIC) was constructed. After modified with Ad-OIC, supernatant of DPSC were co-cultured with HT-22 cells and the effect of DPSC-OIC on the HT-22 cells were evaluated via Cell Counting Kit-8 (CCK-8) assay, Real-Time polymerase chain reaction (PCR) analysis, laser confocal microscopy and fluorescence activating cell sorter (FACS). DPSC-OIC were injected in the lesion area of injured spinal cord and the survival time of transplanted cells were measured by bioluminescence imaging system. The recovery of the injured spinal cord was evaluated by behavioral score, radiological evaluation and immunopathological analysis. Results: DPSC-OIC could enhance the proliferation and axon growth of HT-22 cells, and protect HT-22 cells from H2O2 induced apoptosis. The transplanted DPSC-Null or DPSC-OIC could survive for more than two weeks in local injection site. DPSC-OIC treatment could increase Basso-Mouse Scale (BMS) scores, improve Magnetic Resonance Imaging (MRI) manifestation and promote bladder function recovery. Less apoptotic neurons and more proliferative cells were found in the lesion area of DPSC-OIC treated spinal cord. Nestin+ cells and neural stem cell marker (Sox2) were both up-regulated after DPSC-OIC treatment. Additionally, inhibitory extracellular matrix proteoglycan Neural/Glial Antigen 2 (NG2) was down-regulated and axon growth promotive factor fibronectin was up-regulated after both DPSC-Null (DPSCs infected with Ad-Null) and DPSC-OIC treatments. Conclusions: DPSC-OIC could be a novel effective method for treating SCI.

Association of triglyceride-glucose index with the risk of prostate cancer: a retrospective study.

Background: Prostate cancer is the most common malignancy in men, and its incidence is increasing year by year. Some studies have shown that risk factors for prostate cancer are related to insulin resistance. The triglyceride-glucose (TyG) index is a marker of insulin resistance. We investigated the validity of TyG index for predicting prostate cancer and the dose-response relationship in prostate cancer in relation to it. Objective: To investigate the risk factors of TyG index and prostate cancer prevalence. Methods: This study was screened from the First Affiliated Hospital of Xinjiang Medical University and included 767 people, including 136 prostate cancer patients in the case group and 631 healthy people in the control group. The relationship between TyG index and the risk of prostate cancer was analyzed by one-way logistic regression, adjusted for relevant factors, and multi-factor logistic regression analysis was performed to further investigate the risk factors affecting the prevalence of prostate cancer. ROC curves and Restricted Cubic Spline were established to determine the predictive value and dose-response relationship of TyG index in prostate cancer. Results: Blood potassium (OR = 0.056, 95% CI [0.021-0.148]), total cholesterol (OR = 1.07, 95% CI [0.792-1.444]) and education level (OR = 0.842, 95% CI [0.418-1.697]) were protective factors for prostate cancer, alkaline phosphatase, age, LDL, increased the risk of prostate cancer (OR = 1.016, 95% CI [1.006-1.026]) (OR = 139.253, 95% CI [18.523-1,046.893] (OR = 0.318, 95% CI [0.169-0.596]); TyG index also was a risk factor for prostate cancer, the risk increased with TyG levels,and persons in the TyGQ3 group (8.373-8.854 mg/dL) was 6.918 times (95% CI [2.275-21.043]) higher than in the Q1 group,in the TyGQ4 group (≥8.854) was 28.867 times of those in the Q1 group (95% CI [9.499-87.727]). Conclusion: TyG index may be a more accurate and efficient predictor of prostate cancer.

Prostate cancer epidemiology and prognostic factors in the United States.

Objective: Using the latest cohort study of prostate cancer patients, explore the epidemiological trend and prognostic factors, and develop a new nomogram to predict the specific survival rate of prostate cancer patients. Methods: Patients with prostate cancer diagnosed from January 1, 1975 to December 31, 2019 in the Surveillance, Epidemiology, and End Results Program (SEER) database were extracted by SEER stat software for epidemiological trend analysis. General clinical information and follow-up data were also collected from 105 135 patients with pathologically diagnosed prostate cancer from January 1, 2010 to December 1, 2019. The factors affecting patient-specific survival were analyzed by Cox regression, and the factors with the greatest influence on specific survival were selected by stepwise regression method, and nomogram was constructed. The model was evaluated by calibration plots, ROC curves, Decision Curve Analysis and C-index. Results: There was no significant change in the age-adjusted incidence of prostate cancer from 1975 to 2019, with an average annual percentage change (AAPC) of 0.45 (95% CI:-0.87~1.80). Among the tumor grade, the most significant increase in the incidence of G2 prostate cancer was observed, with an AAPC of 2.99 (95% CI:1.47~4.54); the most significant decrease in the incidence of G4 prostate cancer was observed, with an AAPC of -10.39 (95% CI:-13.86~-6.77). Among the different tumor stages, the most significant reduction in the incidence of localized prostate cancer was observed with an AAPC of -1.83 (95% CI:-2.76~-0.90). Among different races, the incidence of prostate cancer was significantly reduced in American Indian or Alaska Native and Asian or Pacific Islander, with an AAPC of -3.40 (95% CI:-3.97~-2.82) and -2.74 (95% CI:-4.14~-1.32), respectively. Among the different age groups, the incidence rate was significantly increased in 15-54 and 55-64 age groups with AAPC of 4.03 (95% CI:2.73~5.34) and 2.50 (95% CI:0.96~4.05), respectively, and significantly decreased in ≥85 age group with AAPC of -2.50 (95% CI:-3.43~-1.57). In addition, age, tumor stage, race, PSA and gleason score were found to be independent risk factors affecting prostate cancer patient-specific survival. Age, tumor stage, PSA and gleason score were most strongly associated with prostate cancer patient-specific survival by stepwise regression screening, and nomogram prediction model was constructed using these factors. The Concordance indexes are 0.845 (95% CI:0.818~0.872) and 0.835 (95% CI:0.798~0.872) for the training and validation sets, respectively, and the area under the ROC curves (AUC) at 3, 6, and 9 years was 0.7 or more for both the training and validation set samples. The calibration plots indicated a good agreement between the predicted and actual values of the model. Conclusions: Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.

A retrospective study: analysis of the relationship between lactate dehydrogenase and castration-resistant prostate cancer based on restricted cubic spline model.

Background: Different prostate cancer patients take different amounts of time to progress to castration-resistant prostate cancer (CRPC), and this difference in time determines the patient's ultimate survival time. If the time to progression to CRPC can be estimated for each patient, the treatment can be better individualized. Objective: Castration-resistant prostate cancer is a challenge in attacking prostate cancer, the aim of the paper is to analyze the correlation between lactate dehydrogenase (LDH) and CRPC occurrence based on the restricted cubic spline model, and to provide a theoretical basis for LDH as a prognostic biomarker for prostate cancer patients. Methods: We retrospectively analyzed clinical and follow-up data of patients diagnosed with prostate cancer and treated with Androgen Deprivation Therapy (ADT) in our hospital from October 2019 to August 2022. Investigate the correlation between LDH and CRPC by COX regression, restricted cubic spline model and survival analysis. Results: The initial tPSA concentration, prostate volume, LDH and alkaline phosphatase levels in patients with prostate cancer with rapid progression are higher than those in patients with prostate cancer with slow progression. Multivariate COX regression showed that initial tPSA level and LDH level are independent risk factors for prostate cancer. Restricted cubic spline model further showed that LDH level is linearly correlated with the risk of CRPC in prostate cancer patients (total P < 0.05, nonlinear P > 0.05). Conclusion: LDH was associated with the prognosis of prostate cancer and had a dose-response relationship with the risk of CRPC in prostate caner patients.

Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells.

Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The coculture system included the macrophage cell line RAW264.7 and splenocytes. Reactive oxygen species (ROS) levels and glycolysis in T cells were evaluated. Cinnamaldehyde effectively inhibits cytokine storms both in vitro and in vivo. It decreased inflammatory cytokine (such as IFN-γ, TNF-α, IL-6, and IL-2) production by murine peripheral blood cells upon direct stimulation with ConA, after immunization with the MHV-A59 virus or ORF3a peptide from SARS-CoV-2. Cinnamaldehyde restored the percentage of T cells, which was originally decreased in the peripheral blood and splenocytes of ORF3a-immunized mice. In a coculture system, cinnamaldehyde reduced the secretion of inflammatory cytokines from macrophages in a T-cell dependent manner. Furthermore, cinnamaldehyde decreased the ROS level in activated T cells, which in turn reduced glycolysis and the activation of T cells. Cinnamaldehyde can be used as a candidate molecule for COVID-19.

Preliminary study on miRNA in prostate cancer.

OBJECTIVE: To screen for miRNAs differentially expressed in prostate cancer and prostate hyperplasia tissues and to validate their association with prostate cancer. METHODS: Patients diagnosed by pathology in the Department of Urology of the First Affiliated Hospital of Xinjiang Medical University from October 2021 to June 2022 were selected, and their general clinical information, blood samples, and prostate tissue samples were collected. miRNA microarray technology was performed to obtain differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and miRNAs to be studied were screened by microarray results and review of relevant literature. The detection of miRNA expression in the patients' blood and prostate tissue samples was measured. The miRNA-222-mimics were transfected into PC3 cells, and cell biology experiments such as CCK8, scratch, Transwell, and flow cytometry were performed to detect the effects of overexpressed miRNA-222 on the growth and proliferation, invasive ability, apoptotic ability, and metastatic ability of prostate cancer cells. RESULTS: The results of the miRNA microarray showed that there were many differentially expressed miRNAs in prostate cancer and hyperplasia tissues, and four miRNAs, miRNA-144, miRNA-222, miRNA-1248, and miRNA-3651 were finally selected as the subjects by reviewing relevant literature. The results showed that the expression of miRNA-222 in prostate cancer tissues was lower than that in prostate hyperplasia tissues (P < 0.05). The expression of miRNA-222, miRNA-1248, and miRNA-3651 in blood samples of prostate cancer patients was lower than that in prostate hyperplasia patients (P < 0.05). The analysis results indicated that the f/t ratio and the relative expression of miRNA-222 and miRNA-1248 were independent influences of prostate cancer (P < 0.05), in which overexpression of miRNA-222 decreased the proliferative, invasive, and metastatic abilities of PC3 cells and enhanced the level of apoptosis of cancer cells. CONCLUSIONS: Although there was no significant change in the overall incidence of prostate cancer in this study, significant changes occurred in the incidence of prostate cancer with different characteristics. In addition, the nomogram prediction model of prostate cancer-specific survival rate constructed based on four factors has a high reference value, which helps physicians to correctly assess the patient-specific survival rate and provides a reference basis for patient diagnosis and prognosis evaluation.

Direct Identification and Quantitation of Protein Peptide Powders Based on Multi-Molecular Infrared Spectroscopy and Multivariate Data Fusion.

Given that protein peptide powders (PPPs) from different biological sources were inherited with diverse healthcare functions, which aroused adulteration of PPPs. A high-throughput and rapid methodology, united multi-molecular infrared (MM-IR) spectroscopy with data fusion, could determine the types and component content of PPPs from seven sources as examples. The chemical fingerprints of PPPs were thoroughly interpreted by tri-step infrared (IR) spectroscopy, and the defined spectral fingerprint region of protein peptide, total sugar, and fat was 3600-950 cm-1, which constituted MIR finger-print region. Moreover, the mid-level data fusion model was of great applicability in qualitative analysis, in which the F1-score reached 1 and the total accuracy was 100%, and a robust quantitative model was established with excellent predictive capacity (Rp: 0.9935, RMSEP: 1.288, and RPD: 7.97). MM-IR coordinated data fusion strategies to achieve high-throughput, multi-dimensional analysis of PPPs with better accuracy and robustness which meant a significant potential for the comprehensive analysis of other powders in food as well.

Polysaccharides from Lentinus edodes prevent acquired drug resistance to docetaxel in prostate cancer cells by decreasing the TGF-ß1 secretion of cancer-associated fibroblasts.

Prostate cancer is one of the most prevalent lethal diseases among men globally. In the treatment of prostate cancer, the limited therapeutic efficacy of the standard non-hormonal systemic therapy docetaxel (DTX) represents an important challenge. Cancer-associated fibroblasts (CAFs) play a crucial role in resistance to therapy because of their prevalence and functional pleiotropy in tumor environments. Our previous research revealed that MPSSS, a novel polysaccharide extracted from Lentinus edodes, could significantly attenuate the immunosuppressive function of myeloid suppressor cells and CAFs. In this study, we investigated whether MPSSS could potentiate the efficacy of DTX against prostate cancer by inhibiting CAF-induced chemoresistance and elucidated its underlying mechanisms. The sensitivity of PC-3 prostate cancer cells cultured with conditioned medium derived from CAFs (CAF-CM) to DTX was assessed. The resistance effect induced by CAF-CM was abolished when CAFs were pretreated with MPSSS. Bioinformatic analysis of datasets from the Gene Expression Omnibus database revealed the activation of the transforming growth factor ß1 (TGF-ß1) signaling pathway in DTX-resistant cells. Based on this finding, we demonstrated that treatment with the TGF-ß1 receptor inhibitor SB525334 reversed DTX resistance in CAFs, suggesting that TGF-ß1 secreted by CAFs was a crucial intermediary in the development of DTX resistance in PC3 cells. Further research revealed that MPSSS decreases the secretion of TGF-ß1 by inhibiting the JAK2/STAT3 pathway via Toll-like receptor 4 in CAFs. Overall, MPSSS might be a potential adjuvant treatment for DTX resistance in prostate cancer.

PTPMT1 protects cardiomyocytes from necroptosis induced by γ-ray irradiation through alleviating mitochondria injury.

Radiation-induced heart disease (RIHD) progresses over time and may manifest decades after the initial radiation exposure, which is associated with significant morbidity and mortality. The clinical benefit of radiotherapy is always counterbalanced by an increased risk of cardiovascular events in survivors. There is an urgent need to explore the effect and the underlying mechanism of radiation-induced heart injury. Mitochondrial damage widely occurs in irradiation-induced injury, and mitochondrial dysfunction contributes to necroptosis development. Experiments were performed using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and rat H9C2 cells to investigate the effect of mitochondrial injury on necroptosis in irradiated cardiomyocytes and to further elucidate the mechanism underlying radiation-induced heart disease and discover possible preventive targets. After γ-ray irradiation, the expression levels of necroptosis markers were increased, along with higher oxidative stress and mitochondrial injury. These effects could be abated by overexpression of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1). Inhibiting oxidative stress or increasing the expression of PTPMT1 could protect against radiation-induced mitochondrial injury and then decrease the necroptosis of cardiomyocytes. These results suggest that PTPMT1 may be a new target for the treatment of radiation-induced heart disease.NEW & NOTEWORTHY Effective strategies are still lacking for treating RIHD, with unclear pathological mechanisms. In cardiomyocytes model of radiation-induced injuries, we found γ-ray irradiation decreased the expression of PTPMT1, increased oxidative stress, and induced mitochondrial dysfunction and necroptosis in iPSC-CMs. ROS inhibition attenuated radiation-induced mitochondrial damage and necroptosis. PTPMT1 protected cardiomyocytes from necroptosis induced by γ-ray irradiation by alleviating mitochondrial injury. Therefore, PTPMT1 might be a potential strategy for treating RIHD.

Association of lipid accumulation product and visceral adiposity index with the risk of hypertension among oil workers in Xinjiang, China.

Background: To explore the relationship between lipid accumulation product (LAP) and visceral adiposity index (VAI) and hypertension in oil workers and to evaluate the predictive value of hypertension by gender. Methods: A sample of 2,312 workers aged 18-60 years old with more than one year of service were selected by a whole-group random sampling method in six oil field bases in Karamay City, Xinjiang. Logistic regression combined with restricted cubic spline model was used to analyze the risk of hypertension in different LAP and VAI. The receiver operator characteristic curve (ROC) with different sex LAP and VAI predicting the risk of hypertension were drawn. Results: (1) There were significant differences in age, smoking, alcohol consumption, hypertension, BMI, WC, WHtR, SBP, DBP, TC, TG, HDL, LDL, FPG and Scr among different gender groups (P < 0.001).The prevalence of hypertension was 10.1%, with 13.9% in men and 3.6% in women. The prevalence of hypertension with different individual characteristics was statistically significant (P < 0.05). (2) Lipid accumulation product and visceral adiposity index were positively associated with hypertension (P < 0.001). The risk of hypertension may increase with the increase of lipid accumulation product and visceral adiposity index. After adjusting for age, sex, BMI, Scr, FPG and other factors, the risk of hypertension in the fourth quartile was (OR = 5.69, 95% CI [2.72-11.8]) and (OR = 3.56, 95% CI [2.03-6.23]) compared with the first quartile of lipid accumulation product and visceral adiposity index. (3) ROC results showed: AUC values of 0.658 (95% CI [0.619-0.696]), 0.614 (95% CI [0.574-0.654]), 0.661 (95% CI [0.620-0.703]) and critical values of 43.25, 1.58, 0.13 for LAP, VAI and combined indicators in men; the AUC values of LAP, VAI and combined indicators for women were 0.787 (95% CI [0.710-0.865]), 0.732 (95% CI [0.640-0.825]), 0.792 (95% CI [0.719-0.864]) and the critical values were 35.73, 1.76 and 0.03. Restricted cubic splines showed a nonlinear dose-response relationship between LAP, VAI, and risk of hypertension prevalence (P < 0.01 for overall trend and P < 0.01 for nonlinearity). Conclusions: Lipid accumulation product and visceral adiposity index may be risk factors for hypertension in oil workers. LAP and VAI have certain predictive value for hypertension.

Development and performance evaluations of an HER-2 kit.

Objective To develop a kit for detecting human epidermal growth factor receptor 2 (HER-2) in the human body. Methods The HER-2 kit was evaluated based on an automated magnetic particle chemiluminescence platform. The kit was developed using the double antibody sandwich-complexation method. Results The kit showed a linear range of 0.01-800 ng/mL, with a linear R2 of >0.999. The limit of the blank was 0.0039 ng/mL, and the precision at 1.00 ng/mL was 9.4%. The recovery rate at 10.00 ng/mL was 97.81-101.81%. The negative serum reference range was 0-8.23 ng/mL. Conclusions The kit had a wide linear range, high accuracy, good precision, and high sensitivity, indicating that it has good application prospects.

Ginger polysaccharide promotes myeloid-derived suppressor cell apoptosis by regulating lipid metabolism.

Recently, targeting myeloid-derived suppressor cells (MDSCs) which mainly play an immunosuppressive role in tumor microenvironment has become a hot spot in tumor immunotherapy. This study focuses on biological effect of ginger polysaccharide extracted from natural plants on promoting apoptosis of MDSCs by regulating lipid metabolism. An MTT assay was used to detect the inhibitory effect of ginger polysaccharide on the growth of an MDSC-like cell line (MSC-2). The apoptosis-promoting effect of ginger polysaccharide on MSC-2 cells was detected by flow cytometry. Expression levels of apoptosis proteins (caspase 9 and Bcl-2) and lipid metabolism enzymes (fatty acid synthase (FASN) and diacylglycerol acyltransferase 2) in MSC-2 cells treated with different concentrations of ginger polysaccharide were detected by western blot assay. Nile red staining was used to quantitatively detect the effect of ginger polysaccharide on lipid droplet synthesis. Ginger polysaccharide inhibited proliferation of MSC-2 cells and promoted their apoptosis by upregulating pro-apoptotic caspase 9 protein, downregulating anti-apoptotic Bcl-2 protein, inhibiting expression of FASN and diacylglycerol acyltransferase 2 (key enzymes in fatty acid synthesis and lipid droplet formation, respectively). Ginger polysaccharide promoted apoptosis of MDSCs by regulating key lipid metabolism enzymes, inhibiting fatty acid synthesis and lipid droplet accumulation, and reducing the energy supply of cells.

Fibroblasts and mouse breast cancer cells can form cellular aggregates in improved soft agar culture medium.

We aimed to build cellular aggregates of TS/A and normal fibroblasts (LX-2) or CAFs (ME-iLX-2), verifying the value of this model in the screening of anticancer drugs and demonstrating the effect of CD44 on aggregate formation. We improved soft agar culture medium to coculture CAFs (NFs) and TS/A and compared the amount and area of cellular aggregates. Eugenol was added to this model to test its value. The transcription of human CD44 was analyzed through RT-qPCR. Cellular aggregates were formed, and both the amount and area of aggregates in the TS/A-ME-iLX-2 coculture group were higher than those in other groups. The eugenol inhibited the formation of TS/A-fibroblasts aggregates. Human CD44 was highly transcripted in TS/A-ME-iLX-2 aggregates. Cocultured cellular aggregates of fibroblasts and TS/A were successfully formed in the improved soft agar culture medium, and the promotion effect of CAFs on cancer cells was further confirmed. The eugenol test showed its value in the screening of anticancer drugs. The RT-qPCR results demonstrated the important effect of CD44 on aggregate formation.

Triglyceride-glucose index is a predictor of the risk of prostate cancer: a retrospective study based on a transprostatic aspiration biopsy population.

Background: Current research suggests that prostate cancer (PCa), one of the most common cancers in men, may be linked to insulin resistance (IR).Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We investigated the relationship between the TyG index and the risk of PCa. Objective: To assess the correlation and dose-response relationship between TyG index and prostate cancer. Method: Retrospectively, 316 patients who required prostate biopsy puncture in the First Affiliated Hospital of Xinjiang Medical University from March 2017 to July 2021 were collected, and the relationship between factors such as the TyG index and prostate cancer was analyzed by Logistic regression model combined with a restricted cubic spline. Results: (1) The differences in age, initial PSA and TyG index between the two groups were statistically significant; (2) Logistic regression results showed that the risk of prostate cancer in the highest quartile of the TyG index (Q4) was 3.387 times higher than that in the lowest quartile (Q1) (OR=3.387,95% CI [1.511,7.593], P=0.003); (3) The interaction results showed a significant interaction between the TyG index Q4 group and age with the risk of developing prostate cancer (P for interaction<0.001). (4) The results of the restricted cubic spline showed a linear dose-response relationship between the TyG index and the risk of prostate cancer; (5) The Receiver operating characteristic (ROC) curve results showed that the area under the curve (AUC) of the TyG index combined with initial PSA and age was 0.840, with a sensitivity and specificity of 62.5% and 93.3%, respectively. Conclusion: TyG index and age are risk factors for prostate cancer, and the interaction between the TyG index and different risk factors may increase the risk of prostate cancer. TyG index has some predictive value for the risk of prostate cancer, and the risk of prostate cancer can be reduced by controlling the levels of blood lipids and blood glucose.

Metabolic syndrome and metastatic prostate cancer correlation study, a real-world study in a prostate cancer clinical research center, Xinjiang, China.

Objective: The aim of this study was to investigate the relevance of metabolic syndrome (MetS) and metabolic scores to the occurrence, progression and prognosis of metastatic prostate cancer (mPCA), assessing the definition of the variables of metabolic syndrome, and the potential mechanisms of MetS and mPCA. Methods: Data were obtained from the database of prostate cancer follow-up at the Urology Centre of the First Affiliated Hospital of Xinjiang Medical University (N=1303). After screening by inclusion and exclusion criteria, clinical data of 190 patients diagnosed with mPCA by pathology and imaging from January 2010 to August 2021 were finally included, including 111 cases in the MetS group and 79 cases in the Non-MetS group. Results: The MetS group was higher than the Non-MetS group: T stage, Gleasson score, initial PSA, tumor load, PSA after 7 months of ADT (P<0.05),with a shorter time to progression to CRPC stage(P<0.05)[where the time to progression to CRPC was relatively shorter in the high metabolic score subgroup of the MetS group than in the low subgroup (P<0.05)].Median survival time was significantly shorter in the MetS group than in the Non-MetS group (P<0.05),and there was a correlation with metabolic score, with the higher metabolic score subgroup having a lower survival time than the lower metabolic score subgroup (P<0.05). Conclusion: Those with mPCA combined with MetS had lower PSA remission rates, more aggressive tumors, shorter time to progression to CRPC and shorter median survival times than those with mPCA without MetS.Tumour progression and metabolic score showed a positive correlation, predicting that MetS may promote the progression of mPCA, suggesting that MetS may be a risk factor affecting the prognosis of mPCA.