High-fat diets induce inflammatory IMD/NFκB signaling via gut microbiota remodeling in Drosophila.

High-fat diets (HFDs), a prevailing daily dietary style worldwide, induce chronic low-grade inflammation in the central nervous system and peripheral tissues, promoting a variety of diseases including pathologies associated with neuroinflammation. However, the mechanisms linking HFDs to inflammation are not entirely clear. Here, using a Drosophila HFD model, we explored the mechanism of HFD-induced inflammation in remote tissues. We found that HFDs activated the IMD/NFκB immune pathway in the head through remodeling of the commensal gut bacteria. Removal of gut microbiota abolished such HFD-induced remote inflammatory response. Further experiments revealed that HFDs significantly increased the abundance of Acetobacter malorum in the gut, and the re-association of this bacterium was sufficient to elicit inflammatory response in remote tissues. Mechanistically, Acetobacter malorum produced a greater amount of peptidoglycan (PGN), a well-defined microbial molecular pattern that enters the circulation and remotely activates an inflammatory response. Our results thus show that HFDs trigger inflammation mediated by a bacterial molecular pattern that elicits host immune response.

Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms.

Sex hormone-binding globulin (SHBG) is a serum glycoprotein exhibiting the unique feature of binding sex steroids with high affinity and specificity. Over the past few decades, there have been significant breakthroughs in our understanding of the function and regulation of SHBG. The biological role of SHBG has expanded from being considered a simple sex hormone transporter to being associated with several complex physiological and pathological changes in a variety of target tissues. Many factors can affect the plasma SHBG levels, with fluctuations in circulating levels affecting the development of various diseases, such as increasing the risk of developing breast cancer. This article reviews the clinical significance of changes in circulating SHBG levels in the development of breast cancer and the possible influence of these levels on endocrine drug resistance in hormone receptor-positive breast cancer. Higher levels of plasma SHBG significantly reduce the risk of estrogen receptor-positive breast cancer, especially in postmenopausal women. Moreover, the molecular mechanisms by which SHBG affects breast cancer risk are also summarized in detail. Finally, transcriptomics and proteomics data revealed that SHBG expression in breast tissue can effectively distinguish breast cancer from normal tissue. Additionally, the association between SHBG expression levels and various classical tumor-related pathways was investigated.

Lianhua Qingke Preserves Mucociliary Clearance in Rat with Acute Exacerbation of Chronic Obstructive Pulmonary Disease by Maintaining Ciliated Cells Proportion and Protecting Structural Integrity and Beat Function of Cilia.

Purpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD. Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 µg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and ß-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera. Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF. Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice.

OBJECTIVE: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. METHODS: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. RESULTS: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. CONCLUSION: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

Predictive factors based on the health belief model on cancer screening behaviour in first degree relatives of patients with Lynch syndrome-associated colorectal cancer.

Objectives: This study aimed to investigate colorectal cancer-related knowledge, health beliefs, and screening behaviour in first-degree relatives (FDRs) of patients with Lynch syndrome-associated colorectal cancer (CRC) and explore the predictive factors of screening behaviour based on a health belief model. Methods: This cross-sectional study was conducted in the colorectal department of a Class A tertiary hospital in Guangzhou from December 2017 to December 2019. A total of 265 FDRs of 96 patients with Lynch syndrome-related CRC were selected. The study was conducted in the colorectal department of a tertiary cancer centre in Guangzhou. The demographic questionnaire, the simplified CRC knowledge questionnaire, and the Champion's Health Belief Model Scale were used for evaluation. Data were analyzed using statistical description, between-group comparisons, and binary logistic regression. Results: A total of 160 (60.4%), 61 (23.0%), and 44 (16.6%) of the participants had high, medium, and low levels of knowledge about CRC, respectively; the average overall score of health belief was 121.36 ± 13.02. Sixty-one participants (23.0%) underwent Lynch syndrome-associated cancer screening. The predictive factors of screening behaviour included sex (male), age (older), married status (married), multiple primary cancers of the index patients, and high levels of knowledge and health beliefs (P < 0.05). Conclusions: The knowledge and health beliefs of cancer and cancer screening in FDRs of patients with Lynch syndrome-associated CRC should be improved. Both knowledge and beliefs are critical in promoting their cancer screening behaviour. Interventions should focus on health education and enhance health beliefs of the FDRs for better screening behaviour.

Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) has become one of the leading causes of disa-bility and death in diabetic patients. Restoring blood supply to the hindlimbs, especially by promoting arteriogenesis, is currently the most effective strategy, in which endothelial cells play an important role. Tongxinluo (TXL) has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease. AIM: To investigate the effect of TXL on diabetic PAD and its underlying mechanisms. METHODS: An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice. Laser Doppler imaging and micro-computed tomography (micro-CT) were performed to assess the recovery of blood flow and arteriogenesis. Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology, Western blot analysis, enzyme-linked immuno-sorbent assay and real-time polymerase chain reaction assays. In vitro, human vascular endothelial cells (HUVECs) and human vascular smooth muscle cells (VSMCs) were pretreated with TXL for 4 h, followed by incubation in high glucose and hypoxia conditions to induce cell injury. Then, indicators of HUVEC pyroptosis and function, HUVEC-VSMC interactions and the migration of VSMCs were measured. RESULTS: Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis. TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway. In addition, TXL restored endothelial cell functions, including maintaining the balance of vasodilation, acting as a barrier to reduce inflammation, and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway. Similar results were observed in vitro. CONCLUSION: TXL has a pro-arteriogenic effect in the treatment of diabetic PAD, and the mechanism may be related to the inhibition of endothelial cell pyroptosis, restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

Estrogen-Like Effect of Bazi Bushen Capsule in Ovariectomized Rats.

This study aims to show the estrogen-like effect of Bazi Bushen capsule (BZBS), a Chinese herbal compound, in ovariectomized mice. Female Sprague-Dawley (SD) rats were randomly divided into six groups: a sham-operated group, a model group (OVX), a progynova group, and BZBS groups (1, 2, and 4 d/kg/d). An ovariectomy was performed on all rats except those in the sham-operated group. Micro-computed tomography (micro-CT) scanning, hematoxylin and eosin (H&E) staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) detection were performed after 4 months of BZBS treatment. As a result, compared with the OVX group, rats treated with BZBS showed an increased number and area of trabecular bone and bone marrow cells, and a decreased number of adipose cells. The bone volume, trabecular number, and trabecular thickness of the right tibia in the medication groups increased and the trabecular space decreased. The 17ß-estradiol and serum calcium levels in the medication groups were elevated, but the levels of serum phosphorus, sclerostin, ß-CTX, and TRACP-5b were decreased. In the medication groups, the RANKL and sclerostin levels were decreased, while the osteoprotegerin (OPG) level was increased. In conclusion, this protocol systematically evaluated the therapeutic effects and potential molecular mechanisms of Chinese herbal compounds in ovariectomized rats with a variety of techniques.

Protective Effects and Potential Mechanism of Tongxinluo on Mice with Thromboangiitis Obliterans Induced by Sodium Laurate.

OBJECTIVE: To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms. METHODS: Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1ß and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer. RESULTS: TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1ß, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01). CONCLUSIONS: TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.

Shensong Yangxin Capsule Reduces the Susceptibility of Arrhythmia in db/db Mice via Inhibiting the Inflammatory Response Induced by Endothelium Dysfunction.

Purpose: The aim of our study was to investigate the mechanism by which the Chinese compound Shensong Yangxin Capsule (SSYX) reduces susceptibility to arrhythmia in db/db mice. Methods: The db/db mice without drug treatment served as the model group. Other-treated db/db mice were administered SSYX for 8 weeks. Electrocardiogram (ECG), electrical mapping, pathological changes, immunofluorescence staining, real-time quantitative PCR, and Western blot analyses were then conducted. Results: SSYX decreased arrhythmia susceptibility and shortened the abnormal ECG parameters of db/db mice. Meanwhile, SSYX restored irregular conduction direction and shortened the conduction time of the isolated heart. HE and Masson staining showed that SSYX alleviated inflammatory infiltration and collagen fiber deposition. Western blot showed that SSYX decreased the protein expression of ICAM-1, VCAM-1, and MCP-1 and increased the protein expression of occludin, ZO-1, eNOS, and Cx43. SSYX also increased the content of NO, decreased ET-1, TNF-α, IL-1ß, IL-6, MCP-1, and CCR-2 mRNA expression, and increased Kv 4.2, Kv 4.3, Cav 1.2, and Nav 1.5 mRNA expression. Furthermore, SSYX decreased the fluorescence intensity of F4/80 and iNOS, increased the fluorescence intensity of CD31 and eNOS, and improved the Cx43 and α-actinin connection structure in cardiac tissues. The above therapeutic effects of SSYX were inhibited by L-NAME. Conclusion: SSYX reduced the susceptibility of db/db mice to arrhythmia by inhibiting the inflammatory response and macrophage polarization, and this effect of SSYX occurred through protection of endothelial cell function.

Oxygen-independent alkyl radical nanogenerator enhances breast cancer therapy.

The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2'-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.

A case report of effective treatment of diabetic foot with the integration of traditional Chinese medicine and western medicine.

Diabetic foot has become one of the leading causes of disability and death in diabetic patients. Restoring blood supply to the lower limbs, especially by increasing collateral vessels, is currently the most effective strategy. We report a 70-year-old female patient diagnosed with diabetic foot who was treated with integrated traditional Chinese and Western medicine. Western medicine treatment includes blood glucose control, lipid regulation, plaque stabilization, antiplatelet coagulation and anti-inflammation. Traditional Chinese medicine (TCM) treatment is based on the principles of promoting blood circulation and relieving pain, benefiting Qi and activating blood circulation, including oral Chinese medicine Tongxinluo and electro-acupuncture treatment. The vascular morphology of the patient's lower limbs and the levels of glucolipid metabolism were evaluated before and after treatment. The results showed that after treatment, the patient had increased blood flow in the lower limbs, reduced plaque in the femoral arteries, and improved levels of glucolipid metabolism.

Contrast-enhanced ultrasonography for differential diagnosis of adnexal masses.

Background: Quantitative contrast-enhanced ultrasonography parameters are affected by various factors. We evaluated corrected quantitative contrast enhanced ultrasonography in differentiating benign adnexal tumors from malignant tumors. Methods: Patients with adnexal masses who underwent conventional and contrast-enhanced ultrasonography were included. Contrast-enhanced ultrasonography parameters such as base intensity, arrival time, peak intensity, time to peak intensity, ascending slope, and descending slope were measured. Corrected (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus were calculated. Lesions were confirmed by pathologic examination of surgical specimens. Results: This study included 31 patients with 35 adnexal lesions including 20 (57.10%) benign and 15 (42.90%) malignant lesions. The corrected contrast-enhanced ultrasonography quantitative parameters in lesions were statistically different between malignant and benign groups (P<0.05). The optimal cut-off value for (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus, ascending slope, and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus, and descending slope for differentiating malignant adnexal masses from benign tumors were 1.05 (area under curve: 0.93, P<0.05), 1.11 (area under curve: 0.83, P<0.05), 0.82 (area under curve: 0.73, P<0.05), and -0.27 (area under curve: 0.66, P=0.16), with sensitivity and specificity of 93.33% and 85.00%, 86.67% and 75.00%, 86.67% and 60.00%, and 54.55% and 66.67%, respectively. Conclusions: Corrected contrast-enhanced ultrasonography parameters provide practical differential diagnosis value of adnexal lesions with high reliability for sonologists.

Effects of consuming red furu (fermented bean curd) on serum vitamin B-12, homocysteine and other cardiometabolic risk factors in young healthy volunteers: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: The health benefits of red furu in young, healthy volunteers had not been adequately investigated. The aim of this study was to determine the effect of a single meal containing red furu on serum vitamin B-12 (B-12), homocysteine and other cardiometabolic risk factors compared with that of tofu. METHODS AND STUDY DESIGN: Twenty-three healthy volunteers from Zhejiang University, China, were randomly assigned to two groups of consumption, either red furu (n=11, 5 women and 6 men) or tofu (n=12, 6 women and 6 men). Volunteers consumed one breakfast meal composed of either 50 g of red furu (intervention group) or 50 g of tofu (non-active comparison group) with two slices of bread. Fasting blood was collected at 0 h, 24 h, and 72 h. Standard methods were used to measure the volunteers' biochemical parameters. RESULTS: The consumption of 50 g of red furu a day did not significantly affect serum B-12 and showed a non-significant trend to reduce serum homocysteine. In the red furu group, but not in tofu group, serum concentrations of B-12 and folate were negatively associated with homocysteine, and B-12 was positively associated with folate. CONCLUSIONS: A breakfast meal with 50 g of red furu containing 0.096 µg of B-12 did not increase serum B-12 in healthy volunteers. These results suggested that one meal containing B-12 could be sufficient to reduce serum Hcy.

Ultrasonographic Imaging Features of Female Urethral and Peri-urethral Masses: A Retrospective Study of 95 Patients.

The aim of this study was to assess the imaging features of urethral and peri-urethral masses on transvaginal or transperineal ultrasound (US) in a cohort of 95 women. In this retrospective study, medical records of 95 female patients with 98 asymptomatic or symptomatic urethral and peri-urethral masses were retrospectively reviewed. Data regarding patient demographic characteristics, symptoms, signs, imaging features on 2-D and 3-D transvaginal or transperineal US, diagnostic tests and physical and intra-operative findings were extracted. The US imaging features and clinicopathologic characteristics of each urethral or peri-urethral mass were compared. On ultrasound, 39 masses (in 39 patients) were diagnosed as urethral diverticula, which manifested mostly as complex cystic masses (24/39, 61.5%); 35 masses (in 33 patients) were diagnosed as para-urethral cysts, which manifested mostly as simple cystic masses (19/35, 54.3%); 13 hypo-echoic solid masses (in 12 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral leiomyomas; hypo-echoic or heterogeneous solid masses (in 8 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral caruncles, including one complicated by malignant transformation; solid masses with mixed echogenicity (in 2 patients) exhibiting blood flow signals on color Doppler imaging were diagnosed as urethral squamous cell carcinoma or adenocarcinoma, and a hypoechoic solid mass (in one patient) with blood-flow signals on color Doppler imaging was diagnosed as urethral condyloma associated with human papillomavirus infection. This study confirmed transvaginal or transperineal 2-D and 3-D ultrasonography to be a valid, non-invasive, cost-effective diagnostic modality for the differential diagnosis of urethral and periurethral masses.

Preclinical in vivo imaging for brown adipose tissue.

Brown adipose tissue (BAT) has multiple functions in the human body, including the production of heat and increasing energy consumption. However, BAT is also related to many kinds of diseases, such as obesity and metabolic disorders. The progression of such diseases occurs at the cellular level, and thus, imaging techniques could prove greatly beneficial for determining optimal therapeutic regimens. Currently, positron-emission tomography (PET) is considered to be the gold standard for assessing the function of activated BAT. However, PET also has inherent disadvantages, and, thus, recent efforts have been focused on exploring, and potentially developing, new imaging techniques to better observe BAT and evaluate its metabolic function. Researchers have already achieved promising success with computed tomography, magnetic resonance approaches, ultrasound, new tracers for use in PET, and other imaging techniques through in vivo and in vitro animal experiments. Since, these studies have shown that BAT may serve as an effective therapeutic target for treatment of metabolic dysfunction diseases, the development of an efficient in vivo BAT imaging technique that is applicable to humans will prove to be of great clinical value. In this review, classical PET imaging technique is highlighted as well as the current status of preclinical imaging methods developed for BAT examination.

Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/ß-catenin signaling pathway via regulating miR-519d-3p.

Ovarian cancer has the highest mortality in gynecologic malignancies. LncRNA BLACAT1 serves crucial functions in various cancers, but its role in ovarian cancer has not been investigated. In this article, our team explored the role and the potential regulatory mechanism of BLACAT1 in ovarian cancer. Quantitative RT-PCR showed that BLACAT1 was aberrantly up-regulated in ovarian cancer tissues compared with normal tissues. In vitro, BLACAT1 knockdown induced cell cycle arrest and inhibited the proliferation, migration and invasion of ovarian cancer cells using flow cytometry, MTT and EdU assays, wound healing assay and transwell assay, respectively. Luciferase assay verified the binding relationship between microRNA-519d-3p and lncRNA BLACAT1, and BLACAT1 negatively regulated the expression of miR-519d-3p. We also found that miR-519d-3p overexpression could inhibit ovarian cancer cells proliferation, migration and invasion. Further, Western blot demonstrated that the expression of RPS15A and nuclear ß-catenin expression was markedly reduced by BLACAT1 knockdown, and cytoplasmic ß-catenin level was not obviously affected. In vivo, BLACAT1 knockdown inhibited the tumor growth, and immunohistochemistry showed that ki67 expression was decreased by BLACAT1 suppression. Inhibition of BLACAT1 was sufficient to down-regulate the expression of RPS15A and nuclear ß-catenin but did not cause an obvious change in cytoplasmic ß-catenin expression. Taken together, BLACAT1 knockdown inhibited the progression of ovarian cancer by suppressing the Wnt/ß-catenin signaling pathway via regulating miR-519d-3p. Our work provided a proper understanding of the critical roles of BLACAT1 in ovarian cancer.

Endometrioid adenocarcinoma of the rectovaginal septum with invasion of the rectum: a case report and review of literature.

BACKGROUND: Malignant transformation of endometriosis in the rectovaginal septum is rare and usually misdiagnosed as a colorectal or gynecological tumor. We report a rare case of primary endometrioid adenocarcinoma of the rectovaginal septum with invasion of the rectum. CASE PRESENTATION: A 57-year-old overweight woman presented with vaginal bleeding and self-reported left lower abdominal pain during the previous 2 weeks. Preoperative imaging showed a large pelvic mass with invasion of the rectum, suggestive of a gynecologic malignancy. Multiple endoscopic biopsies and immunohistochemical analyses of specimens was performed. The patient received joint gynecological-surgical laparotomy, and there were no intra- or postoperative complications. The histopathological diagnosis was rectovaginal endometrioid adenocarcinoma with rectum infiltration. The patient received adjuvant chemotherapy and achieved good treatment response, with no early complications. At 12 months after surgery, there was no evidence of recurrence. CONCLUSIONS: A high index of clinical suspicion is required for the diagnosis of endometrioid adenocarcinoma in the rectovaginal septum. Surgery combined with additional chemotherapy or radiotherapy seems to be a standard treatment, and hormonal therapy is optional. The efficacies of other therapies, including targeted medication and immunotherapy, are unknown.

Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Offspring's Pancreas of Gestational Diabetes Rats.

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.

lncRNA BANCR promotes EMT in PTC via the Raf/MEK/ERK signaling pathway.

Thyroid cancer is one of the most common types of cancer in the endocrine system. Among all types of thyroid cancer, papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Long non-coding RNA (lncRNA) BRAF-activated non-protein-coding RNA (BANCR) is a 688-bp-long nucleotide transcript, which was first identified in melanoma. The function of BANCR in thyroid cancer remains unclear. The aim of the present study was to investigate whether BANCR is involved in the development of thyroid cancer. The results indicated that BANCR expression was increased in thyroid tumors compared with in adjacent normal tissues. Among cancer cell lines, the expression level of BANCR differed: BANCR expression in BCPAP cell lines was lower compared with that in CAL-62, WRO and FTC-133 cell lines. Overexpression of BANCR promoted the migration and invasion of BCPAP cells. Additionally, BANCR mediated epithelial-mesenchymal transition (EMT) by regulating the expression of epithelial (E)-cadherin, vimentin and neuronal (N)-cadherin. Overexpression of BANCR in BCPAP cells decreased the expression of E-cadherin and increased the expression of vimentin, N-cadherin, phospho (p)-c-Raf, p-extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MEK)1/2 and p-ERK1/2. Administration of U0126 inhibitor inhibited the regulation of phosphorylation levels by MEK1/2 and ERK1/2. Additionally, U0126 upregulated the expression of E-cadherin and downregulated the expression of vimentin. Taken together, the results of the present study suggest that BANCR induces EMT in PTC through the Raf/MEK/ERK signaling pathway.

The protective effect of polyunsaturated fatty acid intake during pregnancy against embryotoxicity of sodium valproate in mice.

Sodium valproate (VPA) is an anti-epileptic drug, but has a strong embryotoxicity due to its induced disturbance of folate-homocysteine (Hcy) metabolism and fatty acid metabolism. The aim of the present study was to investigate whether polyunsaturated fatty acid (PUFA) intake during pregnancy can relieve the embryotoxicity of VPA. VPA (dose: 500 mg kg-1, concentration: 38.5 mg ml-1) was intraperitoneally injected into pregnant mice on day 8.5 of gestation (E8.5d). PUFA intake significantly decreased fetal mortality and NTD incidence induced by VPA: n-3 long chain PUFAs (n-3 LCPUFAs) in fish oil had the best decreasing effect, followed by C18:3n-3 in flaxseed oil and then C18:2n-6 in corn oil. VPA administration inhibited the mRNA and protein expressions of a series of enzymes involved in folate-Hcy metabolism in the liver of pregnant mice; however, it led to the mRNA and protein overexpression of these enzymes in embryos. An elevated Hcy level in embryos was observed 6 h after VPA injection. n-3 PUFA intake effectively relieved this disturbance of folate-Hcy metabolism in pregnant mice and embryos, and this relieving effect of n-3 LCPUFAs and C18:3n-3 is better than that of C18:2n-6. In addition, n-3 PUFA intake also relieved the growth retardation induced by VPA. In conclusion, PUFA intake during pregnancy can effectively decrease embryotoxicity of VPA by relieving VPA-induced disturbance of folate-Hcy metabolism in pregnant mice and embryos, and n-3 LCPUFA in fish oil had the optimal protection effect.