Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms.

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

Expert consensus on the clinical application of totally implantable venous access devices in the upper arm (2022 Edition).

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

Disruption of the ADAM17/NF-κB feedback loop in astrocytes ameliorates HIV-1 Tat-induced inflammatory response and neuronal death.

A disintegrin and metalloproteinases (ADAMs) are involved in multiple neurodegenerative diseases. However, the roles and mechanisms of ADAMs in HIV-associated neurocognitive disorder (HAND) remain unclear. Transactivator of transcription (Tat) induces inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. In this study, we determined that ADAM17 expression was upregulated during soluble Tat stimulus in HEB astroglial cells. Inhibition of ADAM17 suppressed Tat-induced pro-inflammatory cytokines production and rescued the astrocytes-derived conditioned media (ACM)-mediated SH-SY5Y neural cells apoptosis. Moreover, ADAM17 mediated Tat-triggered inflammatory response in a NF-κB-dependent manner. Conversely, Tat induced ADAM17 expression via NF-κB signaling pathway. In addition, pharmacological inhibition of NF-κB signaling inhibited Tat-induced inflammatory response, which could be rescued by overexpression of ADAM17. Taken together, our study clarifies the potential role of the ADAM17/NF-κB feedback loop in Tat-induced inflammatory response in astrocytes and the ACM-mediated neuronal death, which could be a novel therapeutic target for relief of HAND.

Indwelling experience and coping strategies of upper arm infusion ports in patients with cancer: a qualitative study.

OBJECTIVES: The upper arm infusion ports have been proven to be advanced and safe, but the experience from the perspective of patients is lacking. This study explored the indwelling experience and coping strategies of upper arm infusion ports in patients with cancer. DESIGN: Qualitative exploratory study. SETTING: This study was conducted between May 2021 and August 2021 at a level III-A general hospital in Shanghai, China. PARTICIPANTS: The participants, who are patients with cancer implanted with the upper arm infusion ports, included 10 women and 6 men, and the average age was 54.4±8.3 years old. METHODS: Data were selected from semistructured in-depth interviews and analysed by thematic analysis. RESULTS: There were 10 descriptive topics and 4 analytical topics in 2 parts. The indwelling experience includes positive experience (treatment benefit, life convenience) and negative experience (physical discomfort, social anxiety, psychological distress). Coping strategies include emotional-focused strategies (self-acceptance, avoidance and self-protection) and problem-focused strategies (information seeking, functional exercise and remove as soon as possible). CONCLUSION: The infusion port in the upper arm is beneficial to the safety and quality of life of patients with cancer. At the same time, there are challenges in physical, psychological and social adaptation. Patients respond with some measures, but obstacles may arise during implementation.

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn's disease.

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn's disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.

Pediatric esophagogastroduodenoscopy in china: indications, diagnostic yield, and factors associated with findings.

BACKGROUND: Large-scale data on esophagogastroduodenoscopy (EGD) in China are scarce. This study aimed to assess the indications and diagnostic yield of EGD in children and the relationship between factors (such as age, sex, and indications) and diagnostic yield. METHODS: We performed a prospective cross-sectional observational study involving patients aged < 18 years who underwent diagnostic EGD. The study was conducted in five children's hospitals, each in a different city. Demographic features, indications for endoscopy, and endoscopic and histopathological findings were collected. Univariable and multivariable ordinal logistic regression analyses of the relationship between the factors and diagnostic yield were performed. RESULTS: The study included 2268 patients (male/female ratio, 1.3:1) with a median age of 8.68 years. Among the 2268 children, the most frequent indications were abdominal pain in 1954 (86.2%), recurrent vomiting in 706 (31.1%), weight loss in 343 (15.1%), and others. The endoscopic yield was 62.5% and was the highest in patients with dysphagia (90.9%). The histologic yield was 30.4% and was the highest in patients with unexplained anemia (45.5%). On multivariable regression analysis, the endoscopic yield was associated with dysphagia, gastrointestinal (GI) bleeding, and recurrent vomiting, and the histologic yield was associated with age. Different groups of patients with abdominal pain had variable probabilities of abnormal endoscopic findings. CONCLUSIONS: The most frequent indication of pediatric EGD is abdominal pain, with variable probabilities of abnormal endoscopic findings in different groups. Endoscopic yield and histologic yield are associated with certain alarming features. TRIAL REGISTRATION: The trial registration number (ClinicalTrials. gov): NCT03603093 (The study was registered on 27/07/2018).

Decomposition of Clinical Significance of FSH, LH, E2, AMH, and AFC Standards in Females at Lofty Elevation Based on HIF1α.

Based on hypoxia-inducible factor-1α (HIF-1α), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH), the antral follicle is explored. The expression of count (AFC) in females at lofty elevation and its clinical significance are analyzed. A total of 82 females in lofty elevation areas and in low-elevation areas who received health checks from April 2020 to May 2021 are selected as the lofty elevation set and the low-elevation set, respectively. In addition, 76 females are served as the routine set. By comparing the serum HIF-1α standards, the standards of sex hormone indexes FSH, LH, and E2, and the expressions of AMH and AFC between the two sets of females, the correlation between HIF-1α and sex hormone indexes and ovarian reserve function is analyzed. The experimental results show that the lofty standard of HIF-1α in females at lofty elevation may lead to abnormal standards of sex hormones and weakened ovarian reserve. The detection of HIF-1α in females in lofty elevation areas is of great significance for evaluating their sex hormone standards, ovarian function, and preventing the occurrence of female gynecological diseases.

Kinesiophobia and related factors in cancer patients with TIAPs during the long term: a cross-sectional survey.

OBJECTIVE: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs). METHODS: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia. RESULTS: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia. CONCLUSION: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects.

Protein tyrosine phosphatase receptor type O (PTPRO) knockdown enhances the proliferative, invasive and angiogenic activities of trophoblast cells by suppressing ER resident protein 44 (ERp44) expression in preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, is the primary cause of maternal mortality. This work was designed to investigate the specific functions of PTPRO/ ERp44 in the biological behaviors of trophoblast cells and elucidate the underlying molecular mechanism. Constructed siRNA-PTPRO and ERp44 overexpression plasmids were transfected into HTR-8/SVneo and JEG-3 cells for further functional experiments. Subsequently, the proliferation and invasion of trophoblast cells were identified by performing CCK-8, flow cytometry and transwell assay. In addition, tube formation assay was employed to estimate the angiogenic ability of HUVECs incubated with the conditioned media (CM) of HTR-8/SVneo or JEG-3 cells. Importantly, the interaction between PTPRO and ERp44 was analyzed through Co-IP. In the current investigation, it was discovered that downregulation of PTPRO notably facilitated the proliferation and invasion of trophoblast cells and induced a stronger in vitro angiogenesis. Moreover, PTPRO interacted with ERp44 to regulate ERp44 expression. ERp44 overexpression suppressed the proliferative, invasive and angiogenic activities of trophoblast cells. As a result, functions of PTPRO knockdown in the biological behaviors of trophoblast cells were partially abrogated upon elevation of ERp44. To sum up, this current research systematically evidenced that PTPRO could regulate the biological behaviors of trophoblast cells by modulating ERp44. Findings may contribute to a novel therapeutic strategy for PE.

Efficacy and safety of Kanglaite injection combined with chemotherapy for women breast cancer: A protocol for systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Breast cancer was the second cause of cancer death and approximately accounted for 30% of all newly diagnosed cancer in American women. Adjuvant chemotherapy is the preferred treatment approach for breast patients. Kanglaite injection (KI) was commonly used as adjuvant chemotherapy combined with chemotherapy for women breast cancer which could increase chemotherapy efficacy and alleviate chemotherapy drugs induced adverse events, however, the efficacy and safety for KI combined western medicine remains controversial. Thus, we conducted this protocol of systematic review and meta-analysis to estimate the efficacy and safety of KI combined with western medicine for women breast cancer. METHODS: This study will search electronic database included English medicals databases and Chinese databased up to May 2021. The main outcomes of this study include clinical efficacy rate. Adverse reaction rate, Karnofsky Performance Status and immune function were defined as the secondary outcomes. RESULTS: This protocol study will comprehensively evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer. CONCLUSION: This protocol for systematic review and meta-analysis will evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer, aiming to provide optimal therapy for women breast cancer patients.

HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg-1 ·d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 µM), which was attenuated by co-treatemnt with puerarin (100 µM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 µM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Effect of Exclusive Enteral Nutrition on the Disease Process, Nutrition Status, and Gastrointestinal Microbiota for Chinese Children With Crohn's Disease.

BACKGROUND: The aim of this study was to prospectively study the effect of exclusive enteral nutrition (EEN) treatment on Chinese pediatric Crohn's disease (CD) patients. METHODS: Thirty-one newly diagnosed CD patients were enrolled in this study and treated with EEN for 8 weeks. Twelve healthy controls (HCs) donated their fecal samples. Statistical methods were used to compare the differences. RESULTS: According to the Simple Endoscopic Score for CD (SES-CD) at the end of the EEN treatment, 21 patients with SES-CD ≤4 were classified into the remission group (CD-RE), and 10 patients with SES-CD >4 were classified into the nonremission group (CD-NRE). After EEN therapy, there was a significant decrease in the SES-CD, the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), and fecal calprotectin (FCP) in the CD-RE group (all P < .001). The wPCDAI and FCP also decreased in the CD-NRE group (both P < .05). In terms of nutrition improvement, the CD-RE group patients showed more improvement in weight gain, hemoglobin, and serum albumin level than the CD-NRE group patients (all P < .05). For the microbiota, the CD patients had a lower bacterial diversity and different bacterial community compared with HCs. EEN increased overall diversity and was able to shift the dysbiosis in CD patients toward a healthier state. Absence of improvement in wPCDAI and Shannon index at 2 weeks predicts poor response at the end of EEN. CONCLUSION: EEN can be used in most Chinese pediatric CD patients to induce remission and improve nutrition.

Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner.

OBJECTIVE: To assess the expression levels of IFITM1 in human tissue samples and laryngeal squamous cell carcinoma (LSCC) cells, and to explore the potential mechanisms of IFITM1 in LSCC progression. METHODS: Quantitative PCR and immunohistochemical (IHC) assays were performed to detect IFITM1 expression in 62 LSCC tissues and corresponding normal tissues. We further detected the effects of IFITM1 on the proliferation, migration and invasion of LSCC cells and NF-κB signaling pathway through colony formation assay, wound healing assay and transwell assay, respectively. RESULTS: We demonstrated the possible involvement of IFITM1 in the progression of LSCC. We found the upregulated expression of IFITM1 in human LSCC tissues and cells, and analyzed the correlations between IFITM1 expression and osteopontin. Our data further confirmed that IFITM1 affected cell proliferation, migration, and invasion of LSCC cells via the regulation of NF-κB signaling pathway. CONCLUSIONS: We investigated the potential involvement of IFITM1 in the progression of LSCC, and therefore confirmed that IFITM1 was a potential therapeutic target for LSCC.

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.

BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome. AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity. METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data. RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD. CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

Putative regulators for the continuum of erythroid differentiation revealed by single-cell transcriptome of human BM and UCB cells.

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34-CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP, and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.

Carvacrol protects against diabetes-induced hypercontractility in the aorta through activation of the PI3K/Akt pathway.

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It has been reported that carvacrol (CAR) possesses a wide range of biological activities. The effects of CAR on diabetes-induced vasculopathy remain unknown. In this study, diabetic mice were created by the intraperitoneal injection of streptozotocin (STZ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms. We found that CAR decreased blood glucose levels in diabetic mice. Moreover, CAR ameliorated diabetes-induced aortic morphological alterations, as evidenced by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells (VSMCs) layers. Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia, as evidenced by the relaxation of phenylephrine(PE)-induced vasoconstriction, the decreased expression of smooth muscle (SM)-α-actin, and the increased expression of Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, the PI3K/Akt signaling pathway was inhibited in the aortas of diabetic mice and VSMCs in response to hyperglycemia, while CAR treatment activated the PI3K/Akt signaling pathway. In conclusion, our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility, possibly by activating the PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy.

Hyperoside Attenuates Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Inhibiting Apoptosis in Rats.

PURPOSE: Hepatic ischemia-reperfusion (IR) injury is a serious complication of many clinical conditions, which may lead to liver or multiple organ failure. Hyperoside, a flavonoid compound, has been reported to protect against myocardial and cerebral injury induced by IR. This study aimed to investigate the protective effects of hyperoside on hepatic IR injury in rats. METHODS: Using the 70% hepatic IR injury model, we divided 32 male Wistar rats into 4 groups (n = 8): sham-operated, IR+saline (saline/p.o.), IR+vehicle (carboxy methyl cellulose/p.o.), and IR+hyperoside (50 mg/kg/d/p.o.). At 24 hours after reperfusion, blood and liver tissue were collected. The effects of hyperoside on hepatic IR injury were assessed through tests of serum transaminase, hepatic histopathology, and measurement of markers of oxidative stress and apoptosis. RESULTS: Pretreatment with hyperoside protected the liver from IR injury by a reduction in serum aspartate aminotransferase/alanine aminotransferase levels and a decrease in the severity of histologic changes. Hyperoside treatment also decreased the activity of malondialdehyde, increased the activities of superoxide dismutase and glutathione peroxidase, up-regulated the expression of heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and reduced the apoptotic index after IR injury. A decrease in the expression of caspase-3 and an increase in the ratio of B cell lymphoma 2 to B cell lymphoma 2-associated X also were observed. CONCLUSION: Hyperoside has a protective effect on hepatic IR injury in rats, which may be due to its antioxidant and antiapoptotic properties.