Latest ArticlesTANK binding kinase 1 (TBK1) and IKKε, are new members of the IKK family. They are important regulators of nuclear factor κB (NF-κB) signaling pathway and play an important role in metabolic disease. IKKε and TBK1 not only reduce the sensitivity of β adrenergic receptors to catecholamines in adipocytes of obese mice, reduce the level of second messenger cAMP,but also regulate the regeneration of pancreatic β cells. Blocking the IKKε and TBK1 signaling pathways can promote adipose tissue energy consumption, reduce the expression of chronic inflammatory factors in adipocytes, enhance insulin sensitivity, reduce insulin resistance, reduce body weight, and prevent obesity caused by high fat diet. In this review, we reviewed the structure and function of TBK1 and IKKε, as well as the molecular mechanisms of TBK1 and IKKε in the regulation of metabolism in obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). Finally, we discussed the potential of TBK1and IKKε in the treatment of metabolic diseases.
Objective To explore the expression and clinical significance of GALNT2 protein in lung adenocarcinoma(LAC) based on data mining. Methods GALNT2 gene expression in LAC was analyzed using Oncomine database. UALCAN analysis platform was used to analyze the relationship between GALNT2 gene expression in The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets and clinical features, and KM-plotter website was used to analyze the relationship between GALNT2 gene expression in LAC and prognosis. The mutations of GALNT2 gene in LAC from TCGA dataset were explored using cBioportal online analysis tools. The related protein networks were constructed for function enrichment analysis by using String database. Results The data in the Oncomine database showed that the mRNA expression and DNA copy number variation (CNV) of GALNT2 in LAC tissues were significantly higher than those in normal tissues (P<0.01). The transcription and protein level of GALNT2 in tumor tissues in LAC patients were significantly higher than that in marching tissues,but its expression level had no correlation with the clinical pathological characteristics of patients. A total of 52 samples of 503 LAC samples had GALNT2 gene mutation, and the mutation rate was about 10%. Survival curve analysis showed that the overall survival periods of GALNT2 high expression group and GALNT2 mutation group were shorter than those of GALNT2 low expression group and no mutation group (P<0.01). Multivariate Cox regression analysis showed that the high expression of GALNT2 was an independent risk factor of prognosis in LAC (HR=1.48, P=0.01). String database analysis revealed that GALNT1, RAB6A, RAB6B,DYNC1H1, DYNC1LI1, DCTNs, CAPZAs and mucins had obvious interactions with GALNT2, and these proteins were mainly involved in minus-end-directed organelle transport along microtubule, protein O-linked glycosylation via serine/threonine, O-glycan processing and IL-17 signaling pathway. Conclusions GALNT2 can be highly expressed in LAC tissues, has a high frequency of gene mutation, and may be related to poor prognosis of patients using data mining methods, thus providing a theoretical basis for further research on the role of GALNT2 in the occurrence and progression of LAC.
Objective To observe the effect of rifaximin with Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules on diarrhea-predominant irritable bowel syndrome (IBS-D) in patients with small intestinal bacterial overgrowth (SIBO). Methods From July 2018 to December 2019, 114 IBS-D patients with SIBO were randomly divided into probiotics group (n=64) and combined group (n=50). The probiotics group was treated by Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules, while the combined group was treated by rifaximin with Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules. The treatment lasted for 14 days. After treatment, the symptom and serum cytokines were compared between the two groups. Results Before treatment, there were no significant differences in the symptom and accompanied symptoms between the two groups (P>0.05). After treatment, the frequency of abdominal pain, the degree of abdominal distension, the obstruction of intestinal symptoms in life, the symptom severity scale (SSS) total score, the number of patients with emergency defecation and mucus stool of the two groups were relieved or reduced as compared with pre-treatment,and the degree of abdominal pain, the number of patients with abdominal distension in the combined group were relieved or reduced than those before treatment (P<0.05). At the same time, the combined group was superior to the probiotics group in the degree of abdominal pain, the frequency of abdominal pain, the degree of abdominal distension, the SSS total score, the number of mild cases,and the number of patients with abdominal distension (P<0.05). The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α),D-lactic acid (D-LA) and lipopolysaccharide (LPS) in the two groups were lower than those before treatment, and the levels of IL-6,TNF-α and LPS in combined group were lower than those in probiotics group (P<0.05). The negative conversion rate of SIBO in combined group was higher than that in probiotics group (76.0% vs. 46.9%), and the difference was statistically significant(P<0.05). Conclusions Both Live Combined Bacillus Subtilis and Enterococcus Faecium enteric-coated capsules and rifaximin can reverse SIBO and relieve IBS-D symptoms. The effect of the combination of the two drugs is better than that of the single use of the capsules. IBS-D with SIBO is a reasonable indication for rifaximin.
Objective To investigate the curative effect and possible mechanism of berberine in treatment of rats with acute radiation enteritis. Methods Thirty-two male SD rats were randomly divided into blank control group, model group, berberine group and dexamethasone group (8 rats each). Rats in blank control group received pseudo-irradiation, and in remaining groups were irradiated with 12 Gy 60Co γ ray to establish acute radiation enteritis model. Rats in berberine group were given 50 mg/(kg.d)berberine by gavage, in dexamethasone group were given 0.12 mg/(kg.d) dexamethasone by gavage, and rats in model group and blank control group received gavage with the same amount of normal saline. All the gavage continued for 7 days, then the serum and intestinal tissue of rats were taken and stored for later use. The weight and defecation of rats were observed, HE staining was performed to observe the histopathological changes of rat intestinal tissues and count the number of crypts, Masson staining was used to observe the deposition of collagen fibers in rat intestinal tissues, and ELISA was performed to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β and lipopolysaccharide (LPS). The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in intestinal tissues were detected with test kit. The IEC-6 cells were divided into blank control group,model group, berberine group and dexamethasone group. IEC-6 cells in blank control group received pseudo-irradiation, in the rest groups were used to establish the IEC-6 cell radiation damage model, and each group was added with the corresponding medicine serum and co-cultured. qPCR was performed to detect the expression levels of IEC-6 cytochrome C, Bax, Bcl-2, and caspase-3 mRNA in each group. Results The body weight and defecation of rats in berberine group were better than those in dexamethasone group (P<0.05); no obvious intestinal structure damage was found and the proliferation of collagen fibers reduced significantly in rats of berberine group. The number of intestinal crypts was significantly more in berberine group than in model group (173.67±2.33 vs. 115.67±1.45, P<0.05), while no significant difference on the number of intestinal crypts existed between berberine group and dexamethasone group (P>0.05). The levels of IL-6, TNF-α, IL-1β, and LPS in the intestinal tissues of rats were significantly lower in berberine group than in model group, and the IL-6 level was lower in berberine group than in dexamethasone group (P<0.05). The MDA content was significantly lower and the SOD activity was increased in both berberine group and dexamethasone group than in model group (P<0.05), and the MDA content was lower in berberine group than in dexamethasone group (P<0.05). Compared with model group, the expression levels of Bax, caspase-3 and cytochrome C mRNA in IEC-6 cells decreased significantly in berberine group and dexamethasone group, and of Bcl-2 mRNA increased significantly (P<0.05). But no significant difference existed in the expression levels of Bcl-2, Bax, caspase-3 and cytochrome C mRNA in IEC-6 cells between berberine group and dexamethasone group (P>0.05). Conclusion Berberine can effectively improve the inflammatory response of acute radiation enteritis and protect intestinal crypts, the mechanism may be related to reducing the oxidative stress of intestinal tissues and regulating the expression of apoptosis protein in IEC-6 cells.
Objective To analyze the disease burden of benign prostatic hyperplasia (BPH) in China from 1990 to 2019. Methods Data were obtained from the Global Burden of Disease Study 2019. The prevalence, incidence, years lived with disability(YLD) and their corresponding age-standardized rate were used to compare the burden of BPH between China and the world from 1990 to 2019. In addition, a comparative analysis of YLD among 6 urinary diseases was also performed. Results In 2019,the prevalent cases and incidence cases of BPH in China was approximately 20.34 million and 2.84 million, respectively, and the standardized prevalence rate and standardized incidence rate were 2220.85/100 000 and 280.64/100 000, respectively. In addition,the number of YLD due to BPH was approximately 0.41 million and the standardized YLD rate was 44.04/100 000. Compared with 1990, the prevalent cases, incident cases and YLD increased by 125.06%, 122.38% and 123.93% respectively, while the standardized prevalent rate, standardized incident rate and standardized YLD rate decreased by 14.69%, 10.09% and 14.83%, respectively. In 1990 and 2019, the prevalence rate and YLD rate of BPH in China were the highest in the age group ≥80 years old and increased with age.The incidence rate increased in the age group under 79 years old, but decreased in the age group ≥80 years old. In 2019, the YLD of BPH accounted for 61.15% of the 6 urinary diseases, which was 4.11 times that of prostate cancer. Conclusion The disease burden of BPH in China remains at a high level in 2019. Health concerns and guidance on prevention and control should be strengthened for middle-aged and elderly men.
Objective To analyze the expression of chemerin and Sprouty1 proteins in common psoriasis lesion tissues and their correlation with the severity of the disease. Methods Sixty-eight patients with common psoriasis who received treatment at the dermatology outpatient clinic of the Wuxi Fifth People's Hospital and the Affiliated Hospital of Jiangnan University from February 2018 to November 2020 were selected as the experimental group, and another 68 healthy individuals who underwent physical examination at the dermatology outpatient clinics of the two hospitals during the same period were selected as the control group. The skin lesions of the trunk or limbs of patients with psoriasis vulgaris and normal skin tissues of healthy subjects were collected. Immunohistochemistry and Western blotting were used to detect the expression of chemerin and Sprouty1 protein in skin tissues, and RT-PCR was used to detect the relative expression of chemerin and Sprouty1 mRNA in skin tissues, and Pearson correlation was used to analyze the correlation between the expression of chemerin and Sprouty1 protein with the psoriasis area and severity index (PASI). Results The results of immunohistochemical assay showed that chemerin and Sprouty1 proteins were expressed in the skin tissues of both groups. Chemerin protein was strongly expressed in the adipose tissue of the skin lesions in experimental group, and in the subcutaneous adipose tissue of the control group with a small amount of expression; Sprouty1 protein was expressed in the cell membrane of the granular layer cells of the skin lesions in experimental group with a small amount of expression, and in control group, Sprouty1 protein was strongly expressed in the cell membrane and cytoplasm of the whole epidermal layer cells. The relative expressions of chemerin mRNA (1.478±0.14 vs. 0.858±0.08, P<0.001) and protein (1.138±0.12 vs. 0.789±0.06, P<0.001) were significantly higher in experimental group than in control group, and the relative expressions of Sprouty1 mRNA (0.837±0.04 vs. 1.346±0.09, P<0.001) and protein (0.646±0.05 vs. 1.212±0.12, P<0.001) were significantly lower than that of control group. Pearson correlation analysis showed that the relative expression of chemerin protein was positively correlated with PASI score (r=0.536, P<0.05), and the relative expression of Sprouty1 protein was negatively correlated with PASI score (r=-0.619, P<0.05). Conclusion The relative expression of chemerin and Sprouty1 protein in the lesion tissue of common psoriasis correlated with PASI score.
Osteoarthritis (OA) is a degenerative disease causing irreversible progressive destruction of articular cartilage,and still no effective treatment at present. The development of stem cell technology has brought light to the treatment of OA, but the investigate of using exogenous stem cells to repair or regenerate cartilage faces many difficulties, as the chondroid tissue produced by exogenous stem cells is different from the normal articular cartilage in terms of biological characteristics and function. To solve this problem, researchers have proposed mobilizing endogenous stem cells of articular cartilage to promote self-healing of the defect sites. Although articular cartilage lacks intrinsic reparative ability, numerous studies have confirmed the existence of cartilage-derived stem/progenitor cells (CSPCs) in the superficial zone (SPZ) of cartilage. The research progress of superficial zone cartilage-derived stem/progenitor cells (SPZ-CSPCs) and their roles in OA were reviewed in present paper.
Objectives To study the role and associated potential molecular mechanism of osteopontin/insulin-like growth factor 1 (OPN/IGF1) in the corticospinal tract (CST) regeneration. Methods A total of 28 adult C57BL/6 mice (6-8 weeks old) were randomized into the experimental group (injection of AAV-OPN/IGF1, n=14) and control group (injection of AAV-PLAP, n=14) after training of single pellet retrieval. After received the unilateral pyramidotomy surgery, animals received AAV-OPN/IGF1 or AAV-PLAP at the injury site. Further, we employed the movement behaviour test to evaluate spinal motor recovery at 2-week intervals till 12-week after surgery. The protein kinase Cγ (PKCγ) staining in the dorsal funiculus of the cervical spinal cord indicated surgical efficiency. Lastly, we examined the axon sprouting and expression levels of ribosomal protein S6 kinase (pS6)and insulin-like growth factor receptor (IGFR) in neurons using immunohistochemical staining to study the potential mechanism of OPN/IGF1 to promote axon prouting. Results After evaluating PKCγ staining to indicate surgery effectiveness, a total of ten mice were in the experimental group and eight in the control group. In the mouse unilateral pyramidotomy model, OPN/IGF1 has not much effect on the recovery of motor function compared with the control group. After the overexpression of OPN/IGF1 on cortical neurons, sprouting of the spared CST was increased by the elevated expression of pS6 and IGFR, and the difference was statistically significant (P<0.05). Conclusions OPN/IGF1 promotes the sprouting of the CST by increasing the expression of neuronal IGFR and pS6.
Gut microbiome is a critical contributor to host health. It mostly through production of effector molecules possessing biological activity of catabolism modulates metabolic responses at different organ sites including liver, lung, and brain.Skeletal muscle is considered as the largest organ in the body, playing a pivotal role in voluntary movements, postural maintenance and energy homeostasis. Within the past few years, accumulating evidences have revealed biologically important association between the gut microbiota and skeletal muscle and demonstrated muscle function greatly depend on the bacterial population and structure,resulting in a novel and intriguing concept of "gut-muscle axis". This article aims at reviewing the modulatory effects and potential mechanisms of gut microbiota on skeletal muscle and mechanism of short-chain fatty acids (SCFAs) mediated "gut-muscle axis", as well as making recommendations on future research in order to provide a theoretical reference for improving muscle function and physical performance based on gut microbiota intervention.
Objective To compare the safety and curative effect of video-assisted thoracoscopic surgery (VATS) and traditional thoracotomy in treatment of traumatic hemothorax. Methods The clinical data of 91 patients with hemothorax (received VATS) and 131 patients (received thoracotomy) in the Second Affiliated Hospital of PLA Air Force Military Medical University from January 2012 to December 2018 were retrospectively case-control analyzed. The curative effects between the two groups were compared by propensity score matching (PSM) method, and the risk factors of complications were predicted with multivariate logistic analysis. Results The total incidence of complications in the 222 patients was 22.1%. One patient died in thoracotomy group, whereas no patient died in VATS group. Before PSM, the numbers of fractured ribs, proportions of ribs fixation surgery and blunt injuries were lower (P<0.001) with lower incidence of complications (P=0.008) and shorter hospital length of stay (LOS) (P<0.001) in VATS group than those in thoracotomy group. After 1:1 PSM, 120 patients (60 patients in each group) were selected for further statistical analysis, and no significant difference was then identified between the two groups in the rate of complications and the hospital LOS (P>0.05). Significant statistical differences existed between the two groups in postoperative volume of drainage (P=0.006), drainage time (P=0.008), as well as postoperative hospital LOS (P=0.022) and ICU length of stay (P=0.010). Multivariate logistic analysis showed that the operation mode was not the independent risk factor for postoperative complications of traumatic hemothorax operation (OR=0.848, P=0.755). Conclusions VATS is safe and effective for hemodynamically stable patients with traumatic hemothorax since it can avoid the huge trauma of traditional thoracotomy,accelerate postoperative recovery of patients and shorten their postoperative hospital stay.