Salinity-responsive histone PTMs identified in the gills and gonads of Mozambique tilapia (Oreochromis mossambicus).

BACKGROUND: Histone post-translational modifications (PTMs) are epigenetic marks that can be induced by environmental stress and elicit heritable patterns of gene expression. To investigate this process in an ecological context, we characterized the influence of salinity stress on histone PTMs within the gills, kidney, and testes of Mozambique tilapia (Oreochromis mossambicus). A total of 221 histone PTMs were quantified in each tissue sample and compared between freshwater-adapted fish exposed to salinity treatments that varied in intensity and duration. RESULTS: Four salinity-responsive histone PTMs were identified in this study. When freshwater-adapted fish were exposed to seawater for two hours, the relative abundance of H1K16ub significantly increased in the gills. Long-term salinity stress elicited changes in both the gills and testes. When freshwater-adapted fish were exposed to a pulse of severe salinity stress, where salinity gradually increased from freshwater to a maximum of 82.5 g/kg, the relative abundance of H1S1ac significantly decreased in the gills. Under the same conditions, the relative abundance of both H3K14ac and H3K18ub decreased significantly in the testes of Mozambique tilapia. CONCLUSIONS: This study demonstrates that salinity stress can alter histone PTMs in the gills and gonads of Mozambique tilapia, which, respectively, signify a potential for histone PTMs to be involved in salinity acclimation and adaptation in euryhaline fishes. These results thereby add to a growing body of evidence that epigenetic mechanisms may be involved in such processes.

WTAP/IGF2BP3-mediated GBE1 expression accelerates the proliferation and enhances stemness in pancreatic cancer cells via upregulating c-Myc.

BACKGROUND: Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated. METHODS: The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC. RESULTS: GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition. CONCLUSIONS: Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.

Serial dependence requires visual awareness: Evidence from continuous flash suppression.

The visual system often undergoes a relatively stable perception even in a noisy visual environment. This crucial function was reflected in a visual perception phenomenon-serial dependence, in which recent stimulus history systematically biases current visual decisions. Although serial dependence effects have been revealed in numerous studies, few studies examined whether serial dependence would require visual awareness. By using the continuous flash suppression (CFS) technique to render grating stimuli invisible, we investigated whether serial dependence effects could emerge at the unconscious levels. In an orientation adjustment task, subjects viewed a randomly oriented grating and reported their orientation perception via an adjustment response. Subjects performed a series of three type trial pairs. The first two trial pairs, in which subjects were instructed to make a response or no response toward the first trial of the pairs, respectively, were used to measure serial dependence at the conscious levels; the third trial pair, in which the grating stimulus in the first trial of the pair was masked by a CFS stimulus, was used to measure the serial dependence at the unconscious levels. One-back serial dependence effects for the second trial of the pairs were evaluated. We found significant serial dependence effects at the conscious levels, whether absence (Experiment 1) or presence (Experiment 2) of CFS stimuli, but failed to find the effects at the unconscious levels, corroborating the view that serial dependence requires visual awareness.

The mutation rate of rpoB gene showed an upward trend with the increase of MIRU10, MIRU39 and QUB4156 repetitive number.

BACKGROUND: Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) is a frequently used typing method for identifying the Beijing genotype of Mycobacterium tuberculosis (Mtb), which is easily transformed into rifampicin (RIF) resistance. The RIF resistance of Mtb is considered to be highly related with the mutation of rpoB gene. Therefore, this study aimed to analyze the relationship between the repetitive number of MIRU loci and the mutation of rpoB gene. METHODS: An open-source whole-genome sequencing data of Mtb was used to detect the mutation of rpoB gene and the repetitive number of MIRU loci by bioinformatics methods. Cochran-Armitage analysis was performed to analyze the trend of the rpoB gene mutation rate and the repetitive number of MIRU loci. RESULTS: Among 357 rifampicin-resistant tuberculosis (RR-TB), 304 strains with mutated rpoB genes were detected, and 6 of 67 rifampicin susceptible strains were detected mutations. The rpoB gene mutational rate showed an upward trend with the increase of MIRU10, MIRU39, QUB4156 and MIRU16 repetitive number, but only the repetitive number of MIRU10, MRIU39 and QUB4156 were risk factors for rpoB gene mutation. The Hunter-Gaston discriminatory index (HGDI) of MIRU10 (0.65) and QUB4156 (0.62) was high in the overall sample, while MIRU39 (0.39) and MIRU16 (0.43) showed a moderate discriminatory Power. CONCLUSION: The mutation rate of rpoB gene increases with the addition of repetitive numbers of MIRU10, QUB4156 and MIRU39 loci.

Association between obstructive sleep apnea and gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: We aim to conduct a systematic review and determine the association between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD). METHODS: Literature search for eligible studies was performed across major databases. The main endpoint was to assess the association between GERD and OSA. Subgroup analyses were performed to determine this strength of the association stratified by the diagnostic tools used for OSA (nocturnal polysomnogram or Berlin questionnaire) and GERD (validated reflux questionnaire or esophagogastroduodenoscopy). We also compared sleep efficiency, apnea hypopnea index, oxygen desaturation index, and Epworth Sleepiness Scale in OSA patients with or without GERD. Results were pooled together using Reviewer Manager 5.4. RESULTS: Six studies involving 2950 patients with either GERD or OSA were included in the pooled analysis. Our findings suggest that there was a statistically significant unidirectional association between GERD and OSA (odds ratio [OR] = 1.53, P = 0.0001). Subgroup analyses redemonstrated an OSA-GERD association irrespective of the tools used for diagnosing either GERD or OSA (P = 0.24 and P = 0.82, respectively). Sensitivity analyses demonstrated the same association after controlling for gender (OR = 1.63), BMI (OR = 1.81), smoking (OR = 1.45), and alcohol consumption (OR = 1.79). In patients with OSA, there were no statistically significant differences between patients with or without GERD in terms of apnea hypopnea index (P = 0.30), sleep efficiency (P = 0.67), oxygen desaturation index (P = 0.39), and Epworth Sleepiness Scale (P = 0.07). CONCLUSION: There exists an association between OSA and GERD that is independent of the modalities used for screening or diagnosing both disorders. However, the presence of GERD did not affect the severity of OSA.

Age and sex trend differences in hemoglobin levels in China: a cross-sectional study.

BACKGROUND: Both age and gender are the influence factors of hemoglobin concentration. However, the changing trend of hemoglobin levels between males and females with age remains unclear. This study aimed to explore their changing characteristics in different genders. METHODS: A cross-sectional study was conducted in Physical Examination Center of the First Affiliated Hospital of Wannan Medical College in Wuhu, China from 2014 to 2016. The generalized linear model was applied to explore the relationship between age, gender and hemoglobin levels. RESULTS: Among the 303,084 participants, the mean age for females and males was 46.9 ± 13.4(15-98) and 48.1 ± 13.7(14-98) years old, respectively. Generalized smoothing splines showed that hemoglobin levels increased up to age 25 and then decreased in men; in women the levels increased up until age 20, and then decreased, with slight increase again (ß = 0.244, P < 0.01). After dividing all participants into hyperglycemia and normal groups, only the normal female group showed a significant upward trend (ß = 0.257, P < 0.01) between ages 50-59. CONCLUSIONS: Hemoglobin concentration changes with age and the curve is different in males and females. The slightly upward trend of female hemoglobin in the age range of 50-59 years old should be considered in developing the reference range of hemoglobin making.

Glucose oxidase and metal catalysts combined tumor synergistic therapy: mechanism, advance and nanodelivery system.

Cancer has always posed a significant threat to human health, prompting extensive research into new treatment strategies due to the limitations of traditional therapies. Starvation therapy (ST) has garnered considerable attention by targeting the primary energy source, glucose, utilized by cancer cells for proliferation. Glucose oxidase (GOx), a catalyst facilitating glucose consumption, has emerged as a critical therapeutic agent for ST. However, mono ST alone struggles to completely suppress tumor growth, necessitating the development of synergistic therapy approaches. Metal catalysts possess enzyme-like functions and can serve as carriers, capable of combining with GOx to achieve diverse tumor treatments. However, ensuring enzyme activity preservation in normal tissue and activation specifically within tumors presents a crucial challenge. Nanodelivery systems offer the potential to enhance therapy effectiveness by improving the stability of therapeutic agents and enabling controlled release. This review primarily focuses on recent advances in the mechanism of GOx combined with metal catalysts for synergistic tumor therapy. Furthermore, it discusses various nanoparticles (NPs) constructs designed for synergistic therapy in different carrier categories. Finally, this review provides a summary of GOx-metal catalyst-based NPs (G-M) and offers insights into the challenges associated with G-M therapy, delivery design, and oxygen (O2) supply.

Drinking and feasting are perceived as facilitating cooperation.

We argue that the occurrence of puritanical norms cannot simply be explained by appealing to the need for cooperation. Anthropological and archaeological studies suggest that across history and cultures' self-indulgent behaviours, such as excessive drinking, eating, and feasting, have been used to enhance cooperation by enforcing social and group identities.

Prediction of carotid plaque by blood biochemical indices and related factors based on Fisher discriminant analysis.

OBJECTIVE: This study aims to establish the predictive model of carotid plaque formation and carotid plaque location by retrospectively analyzing the clinical data of subjects with carotid plaque formation and normal people, and to provide technical support for screening patients with carotid plaque. METHODS: There were 4300 subjects in the ultrasound department of Maanshan People's Hospital collected from December 2013 to December 2018. We used demographic and biochemical data from 3700 subjects to establish predictive models for carotid plaque and its location. The leave-one-out cross-validated classification, 600 external data validation, and area under the receiver operating characteristic curve (AUC) were used to verify the accuracy, sensitivity, specificity, and application value of the model. RESULTS: There were significant difference of age (F = - 34.049, p < 0.01), hypertension (χ2 = 191.067, p < 0.01), smoking (χ2 = 4.762, p < 0.05) and alcohol (χ2 = 8.306, p < 0.01), Body mass index (F = 15.322, p < 0.01), High-density lipoprotein (HDL) (F = 13.840, p < 0.01), Lipoprotein a (Lp a) (F = 52.074, p < 0.01), Blood Urea Nitrogen (F = 2.679, p < 0.01) among five groups. Prediction models were built: carotid plaque prediction model (Model CP); Prediction model of left carotid plaque only (Model CP Left); Prediction model of right carotid plaque only (Model CP Right). Prediction model of bilateral carotid plaque (Model CP Both). Model CP (Wilks' lambda = 0.597, p < 0.001, accuracy = 78.50%, sensitivity = 78.07%, specificity = 79.07%, AUC = 0.917). Model CP Left (Wilks' lambda = 0.605, p < 0.001, accuracy = 79.00%, sensitivity = 86.17%, specificity = 72.70%, AUC = 0.880). Model CP Right (Wilks' lambda = 0.555, p < 0.001, accuracy = 83.00%, sensitivity = 81.82%, specificity = 84.44%, AUC = 0.880). Model CP Both (Wilks' lambda = 0.651, p < 0.001, accuracy = 82.30%, sensitivity = 89.50%, specificity = 72.70%, AUC = 0.880). CONCLUSION: Demographic characteristics and blood biochemical indexes were used to establish the carotid plaque and its location discriminant models based on Fisher discriminant analysis (FDA), which has high application value in community screening.

Ciprofloxacin and enrofloxacin can cause reproductive toxicity via endocrine signaling pathways.

Ciprofloxacin (CIP) and enrofloxacin (ENR) are veterinary antibiotics commonly utilized to treat and prevent animal diseases. Environmental and dietary antibiotic residues can directly and indirectly affect the reproductive development of animals and humans. This article investigated the reproductive toxicity of CIP in male zebrafish, showing that it could decrease the spermatogonial weight and damage the spermatogonial tissue. The sex hormone assays showed that CIP decreased fshb and lhb gene expression and plasma testosterone (T). In addition, transcriptome analysis indicated that the effect of CIP on zebrafish might be related to the endocrine signaling pathways. ENR, which was selected for further study, inhibited mouse Leydig (TM3) and Sertoli (TM4) cell proliferation and caused cell cycle arrest. The sperm concentration, serum luteotropic hormone (LH) and follicle-stimulating hormone (FSH), and T levels decreased in adolescent mice after ENR treatment for 30d in vivo. Hematoxylin and eosin (H&E) staining showed that ENR exposure potentially induced testicular injury, while the real-time quantitative PCR (qPCR) results indicated that ENR inhibited the mRNA expression of key genes in the Leydig cells (cyp11a1, 3ß-HSD, and 17ß-HSD), Sertoli cells (Inhbß and Gdnf) and spermatogenic cells (Plzf, Stra8 and Dmc1). In conclusion, these findings indicated that ENR exposure might influence the development of the testes of pubescent mice.

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

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

Oxygenation reactions catalyzed by the F557V mutant of soybean lipoxygenase-1: Evidence for two orientations of substrate binding.

Plant lipoxygenases oxygenate linoleic acid to produce 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HPOD) or 9-hydroperoxy-10E,12Z-octadecadienoic acid (9(S)-HPOD). The manner in which these enzymes bind substrates and the mechanisms by which they control regiospecificity are uncertain. Hornung et al. (Proc. Natl. Acad. Sci. USA96 (1999) 4192-4197) have identified an important residue, corresponding to phe-557 in soybean lipoxygenase-1 (SBLO-1). These authors proposed that large residues in this position favored binding of linoleate with the carboxylate group near the surface of the enzyme (tail-first binding), resulting in formation of 13(S)-HPOD. They also proposed that smaller residues in this position facilitate binding of linoleate in a head-first manner with its carboxylate group interacting with a conserved arginine residue (arg-707 in SBLO-1), which leads to 9(S)-HPOD. In the present work, we have tested these proposals on SBLO-1. The F557V mutant produced 33% 9-HPOD (S:R = 87:13) from linoleic acid at pH 7.5, compared with 8% for the wild-type enzyme and 12% with the F557V,R707L double mutant. Experiments with 11(S)-deuteriolinoleic acid indicated that the 9(S)-HPOD produced by the F557V mutant involves removal of hydrogen from the pro-R position on C-11 of linoleic acid, as expected if 9(S)-HPOD results from binding in an orientation that is inverted relative to that leading to 13(S)-HPOD. The product distributions obtained by oxygenation of 10Z,13Z-nonadecadienoic acid and arachidonic acid by the F557V mutant support the hypothesis that ω6 oxygenation results from tail-first binding and ω10 oxygenation from head-first binding. The results demonstrate that the regiospecificity of SBLO-1 can be altered by a mutation that facilitates an alternative mode of substrate binding and adds to the body of evidence that 13(S)-HPOD arises from tail-first binding.

N-linoleoylamino acids as chiral probes of substrate binding by soybean lipoxygenase-1.

Lipoxygenases catalyze the oxygenation of polyunsaturated fatty acids and their derivatives to produce conjugated diene hydroperoxides. Soybean lipoxygenase-1 (SBLO-1) has been the subject of intensive structural and mechanistic study, but the manner in which this enzyme binds substrates is uncertain. Previous studies suggest that the fatty acyl group of the substrate binds in an internal cavity near the catalytic iron with the polar end at the surface of the protein or perhaps external to the protein. To test this model, we have investigated two pairs of enantiomeric N-linoleoylamino acids as substrates for SBLO-1. If the amino acid moiety binds external to the protein, the kinetics and product distribution should show little or no sensitivity to the stereochemical configuration of the amino acid moiety. Consistent with this expectation, N-linoleoyl-l-valine (LLV) and N-linoleoyl-d-valine (LDV) are both good substrates with kcat/Km values that are equal within error and about 40% higher than kcat/Km for linoleic acid. Experiments with N-linoleoyl-l-tryptophan (LLT) and N-linoleoyl-d-tryptophan (LDT) were complicated by the low critical micelle concentrations (CMC = 6-8 µM) of these substances. Below the CMC, LDT is a better substrate by a factor of 2.7. The rates of oxygenation of LDT and LLT continue to rise above the CMC, with modest stereoselectivity in favor of the d enantiomer. With all of the substrates tested, the major product is the 13(S)-hydroperoxide, and the distribution of minor products is not appreciably affected by the configuration of the amino acid moiety. The absence of stereoselectivity with LLV and LDV, the modest magnitude of the stereoselectivity with LLT and LDT, and the ability micellar forms of LLT and LDT to increase the concentration of available substrate are all consistent with the hypothesis that the amino acid moiety binds largely external to SBLO-1 and interacts with it only weakly.

The research progress on the impact of antibiotics on the male reproductive system.

Antibiotics are extensively utilized in the livestock and poultry industry and can accumulate in animals and the environment, leading to potential health risks for humans via food and water consumption. Research on antibiotic toxicity, particularly their impact as endocrine disruptors on the male reproductive system, is still in its nascent stages. This review highlights the toxic effect of antibiotics on the male reproductive system, detailing the common routes of exposure and the detrimental impact and mechanisms of various antibiotic classes. Additionally, it discusses the protective role of food-derived active substances against the reproductive toxicity induced by antibiotics. This review aims to raise awareness about the reproductive toxicity of antibiotics in males and to outline the challenges that must be addressed in future research.

Construction and in vitro evaluation of pH-sensitive nanoparticles to reverse drug resistance of breast cancer stem cells.

Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (ß-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer.

Hedgehog pathway and cancer: A new area (Review).

In years of research on classical pathways, the composition, information transmission mechanism, crosstalk with other pathways, and physiological and pathological effects of hedgehog (HH) pathway have been gradually clarified. HH also plays a critical role in tumor formation and development. According to the update of interpretation of tumor phenotypes, the latest relevant studies have been sorted out, to explore the specific mechanism of HH pathway in regulating different tumor phenotypes through gene mutation and signal regulation. The drugs and natural ingredients involved in regulating HH pathway were also reviewed; five approved drugs and drugs under research exert efficacy by blocking HH pathway, and at least 22 natural components have potential to treat tumors by HH pathway. Nevertheless, there is a deficiency of existing studies. The present review confirmed the great potential of HH pathway in future cancer treatment with factual basis.

Promoting Electrochemical Nitrate Reduction to Ammonia on Silver Nanocrystals Doped with Iron Series Elements.

Electrochemical nitrate reduction to ammonia (NRA) is a promising approach to remove environmental pollutants while producing green NH3 under ambient conditions. Ag-based nanomaterials have been used in NRA but their iron series elements (Fe, Co, Ni) doping has not been explored yet. Herein, an effective and versatile doping strategy of Ag nanocrystals by iron series elements for efficient NRA is presented. Experimental results show that doping with Fe, Co or Ni can improve the NRA activity. Among the catalysts, AgCo delivers the best performance with a Faraday efficiency (FE) of 88.3 % and ammonia selectivity of 97.4 % at-0.23 V vs RHE, which is 1.9 and 6.2 times higher than that of plain Ag (46.4 % FE and 15.8 % selectivity), respectively. A highest NO3 - conversion rate of AgCo (91.8 %) is achieved, which maintains 16.4 ppm NO3 --N in 4 hours, meeting the drinking water level (~15 ppm NO3 --N). Moreover, the FE, selectivity, conversion rate of AgCo do not decay after the four consecutive cycles. It is found that Co doping can effectively induce the change of Ag d-band center for optimized NRA. This work reveals doping effects of iron series elements on Ag-based catalysts, and shows potential practical application in NRA.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies.

OBJECTIVE: To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF). METHODS: Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting. RESULTS: The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs. CONCLUSIONS: STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

Diagnostic Implications of Irritable Bowel Syndrome Is an Independent Risk Factor for Undergoing Surgical Interventions in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can present with overlapping symptoms, making diagnosis and management challenging. Patients with IBD in remission may continue to experience IBS symptoms. Patients with IBS were found to have a disproportionately higher prevalence of abdominal and pelvic surgeries than the general population. AIMS: The aim of this study was to determine whether IBS is a risk factor for undergoing surgical interventions in patients with IBD and explore the diagnostic implications of these findings. METHODS: A population-based cohort analysis was performed using TriNetX. Patients with Crohn's disease + IBS (CD + IBS) and ulcerative colitis + IBS (UC + IBS) were identified. The control groups consisted of patients with CD or UC alone without IBS. The main outcome was to compare the risks of undergoing surgical interventions between the cohorts. The secondary outcomes were to compare the risks of developing gastrointestinal symptoms and IBD-related complications between the cohorts. RESULTS: Patients with IBD who subsequently developed IBS were more likely to experience gastrointestinal symptoms than those without IBS (p < 0.0001). Patients with concomitant IBD and IBS were more likely to develop IBD-related complications, including perforation of the intestine, gastrointestinal bleeding, colon cancer, and abdominal abscess (p < 0.05). Patients with concomitant IBD and IBS were more likely to undergo surgical interventions than patients without IBS, including colectomy, appendectomy, cholecystectomy, exploratory laparotomy, and hysterectomy (p < 0.05). CONCLUSIONS: IBS appears to be an independent risk factor for patients with IBD to develop IBD-related complications and undergo surgical interventions. Patients with concomitant IBD and IBS could represent a unique subgroup of IBD patients with more severe symptoms, highlighting the importance of accurate diagnosis and management in this population.

Multiple Sclerosis Is Associated With Achalasia and Diffuse Esophageal Spasm.

Background/Aims: Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES. Methods: Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study. Results: Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms. Conclusions: Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.