Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease.

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.

The therapeutic effects of saikosaponins on depression through the modulation of neuroplasticity: From molecular mechanisms to potential clinical applications.

Depression is a major global health issue that urgently requires innovative and precise treatment options. In this context, saikosaponin has emerged as a promising candidate, offering a variety of therapeutic benefits that may be effective in combating depression. This review delves into the multifaceted potential of saikosaponins in alleviating depressive symptoms. We summarized the effects of saikosaponins on structural and functional neuroplasticity, elaborated the regulatory mechanism of saikosaponins in modulating key factors that affect neuroplasticity, such as inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the brain-gut axis. Moreover, this paper highlights existing gaps in current researches and outlines directions for future studies. A detailed plan is provided for the future clinical application of saikosaponins, advocating for more targeted researches to speed up its transition from preclinical trials to clinical practice.

Turmeric and curcuminiods ameliorate disorders of glycometabolism among subjects with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Metabolic diseases are globally popular, and a systematic review and meta-analysis of turmeric and curcuminoids on glucose metabolism among people with metabolic diseases was performed. DESIGN: We comprehensively searched Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, the Cochrane Library and two Chinese databases, Wanfang and CNKI for RCTs that focused on the effects of turmeric and curcuminoids on fasting blood glucose (FBG), hemoglobin A1C (HbA1c), fasting serum insulin (FSI) and HOMA-IR among patients with metabolic diseases. The FBG and HbA1c were the main outcomes to be analyzed. With random-effects models, separate meta-analyses were conducted by inverse-variance and reported as WMD with 95% CIs. RESULTS: Evidence from 17 RCTs including 22 trials showed that turmeric and curcuminoids lowered FBG by - 7.86 mg/dL (95% CI: -12.04, -3.67 mg/dL; P = 0.0002), HbA1c by - 0.38% (95% CI: -0.52%, -0.23%; P < 0.00001) and HOMA-IR by - 1.01 (95% CI: -1.6, -0.42; P = 0.0008). Moreover, they decreased fasting serum insulin by - 1.69 mU/L (95% CI: -3.22, -0.16 mU/L; P = 0.03) after more than 8 weeks of intervention in a subgroup analysis. CONCLUSIONS: Turmeric and curcuminiods decrease FBG, HbA1c and HOMA-IR significantly among subjects with metabolic disease. Additionally, they may have an effect on FSI concentrations if the intervention period is more than 8 weeks. However, attention should be paid to these outcomes due to the significant heterogeneity.

Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway.

Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1ß and TNF-α in the serum and downregulated nuclear factor κB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.

The effect and mechanism of Jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis.

BACKGROUND: The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology. METHODS: CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method. RESULTS: The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc. CONCLUSION: Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome.

BACKGROUND: Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. METHODS: Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. RESULTS: One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42-5.552, P = 0.003). CONCLUSIONS: Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

Celastrol alleviates metabolic disturbance in high-fat diet-induced obese mice through increasing energy expenditure by ameliorating metabolic inflammation.

Celastrol, a natural triterpene, has been shown to treat obesity and its related metabolic disorders. In this study, we first assessed the relationship between the antiobesity effects of celastrol and its antiinflammatory activities. Our results showed that celastrol can reduce weight gain, ameliorate glucose intolerance, insulin resistance, and dyslipidemia without affecting food intake in high-fat diet-induced obese mice. A CLAMS was used to clarify the improvement of metabolic profiles was attribute to increased adipose thermogenesis after celastrol treatment. Further studies found that celastrol decreased the infiltration of macrophage as well as its inflammatory products (IL-1ß, IL-18, MCP-1α, and TNF-α) in liver and adipose tissues, which also displayed an obvious inhibition of TLR3/NLRP3 inflammasome molecules. This study demonstrated that celastrol could be a potential drug for treating metabolic disorders, the underlying mechanism is related to ameliorating metabolic inflammation, thus increasing body energy expenditure.

Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study.

BACKGROUND: COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. METHODS: In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. RESULTS: Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. CONCLUSIONS: Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.

Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. Many studies have suggested that lipid overload is the key initial factor that contributes to hepatic steatosis. Our previous study indicated that diosgenin (DSG) has a beneficial effect on energy metabolism, but the underlying mechanism remains unclear. METHODS: Human normal hepatocytes (LO2 cells) were incubated with palmitic acid to establish the cell model of nonalcoholic fatty liver. The effects of DSG on lipid metabolism, glucose uptake and mitochondrial function were evaluated. Furthermore, the mechanism of DSG on oxidative stress, lipid consumption and lipid synthesis in LO2 cells was investigated. RESULTS: The results indicated that palmitic acid induced obvious lipid accumulation in LO2 cells and that DSG treatment significantly reduced the intracellular lipid content. DSG treatment upregulated expression of lipolysis proteins, including phospho-AMP activated protein kinase (p-AMPK), phospho-acetyl-coA carboxylase (p-ACC) and carnitine acyl transferase 1A (CPT-1A), and inhibited expression of lipid synthesis-related proteins, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Additionally, DSG-treated cells displayed a marked improvement in mitochondrial function, with less production of reactive oxygen species and a higher mitochondrial membrane potential compared with the model group. CONCLUSION: This study suggests that DSG can reduce intracellular lipid accumulation in LO2 cells and that the underlying mechanism may be related to the improving oxidative stress, increasing fatty acid ß-oxidation and decreasing lipid synthesis. The above changes might be mediated by the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathway.

Wu-Mei-wan protects pancreatic ß cells by inhibiting NLRP3 Inflammasome activation in diabetic mice.

BACKGROUND: Wu-Mei-Wan (WMW) is a traditional Chinese herbal formulation that is clinically prescribed to treat diabetes mellitus in China. WMW has been shown to alleviate damage in pancreatic ß cells, but the underlying mechanism remains unclear. This study aims to explore how WMW plays a protective role in pancreatic islets. METHODS: Drug testing and mechanism analyses were performed on mice treated with three concentrations of WMW (4800, 9600, and 19,200 mg/kg/bw) for four consecutive weeks. Blood was collected from both db/db and wild-type mice to determine fasting blood glucose (FBG) and serum insulin levels. The expression of proteins related to apoptosis, cysteinyl aspartate-specific proteinase 12 (caspase-12) and B-cell leukemia 2 (Bcl-2), was measured by western blot. Interleukin-1ß (IL-1ß), interleukin-18 (IL-18), monocyte chemoattractant protein-1α (MCP-1α), and tumor necrosis factor-α (TNF-α) in the pancreas were tested with enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry staining of F4/80 was performed to measure the pancreatic infiltration of macrophages. Western blot and immunofluorescence staining of the NLRP3 inflammasome were used to measure the expression of proteins related to apoptosis and inflammation. RESULTS: WMW dose-dependently reduced FBG and promoted serum insulin secretion in db/db mice compared to the wild-type controls. WMW protected pancreatic ß cells with a pattern of decreasing caspase-12 and increasing Bcl-2 expression. WMW also reversed the upregulated production of IL-1ß, IL-18, MCP-1α, and macrophage-specific surface glycoprotein F4/80 in diabetic mice. In addition, the protein expression levels of NLRP3 inflammasome components NLRP3, ASC, and caspase-1 (P20) were higher in db/db mice than in wild-type controls. CONCLUSIONS: WMW inhibits the activation of the NLRP3 inflammasome to protect pancreatic ß cells and prevent type 2 diabetes mellitus development.

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88.

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80+ ratio and CD11c+ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80+CD11c+ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.

The effect of statins on renal outcomes in patients with diabetic kidney disease: A systematic review and meta-analysis.

The effects of statins on renal outcomes in patients with diabetic kidney disease were conflicting. The aim of the study was to investigate whether statins treatment could affect renal outcomes (albuminuria or proteinuria, estimated glomerular filtration rate [eGFR]) for diabetic kidney disease patients. We searched the PubMed, OVID (including MEDLINE and EMBASE), Web of Science and the Cochrane Central Register of Controlled Trials. Randomized controlled trials evaluating the efficacy of statins in diabetic kidney disease patients were selected. The main outcomes were albuminuria (or proteinuria). Secondary outcomes were levels of eGFR. Two authors independently assessed study quality and extracted the information from enrolled trials. Eleven randomized controlled trials with a total number of 543 diabetic kidney disease participants were included in our study. The overall estimates showed that statins statistically reduced albuminuria (standardized mean differences -0.71, 95% CI -1.20 to -0.23, P = .004), though marked heterogeneity was found within studies. However, the analysis results indicated that statins could not reduce overt proteinuria (standardized mean differences -0.14, 95% CI -0.53 to 0.26, P = .49) or slow the rate of reduction in eGFR (standardized mean differences 0.06, 95% CI -0.14 to 0.26, P = .53). In general, our study demonstrated that statins might have beneficial effects on reducing albuminuria in diabetic kidney disease patients. However, there was no strong evidence that the same intervention had an effect on overt proteinuria or eGFR outcomes in these patients.

Jia-Wei-Jiao-Tai-Wan ameliorates type 2 diabetes by improving ß cell function and reducing insulin resistance in diabetic rats.

BACKGROUND: Jia-Wei-Jiao-Tai-Wan (JWJTW), composed of Jiao-Tai-Wan (Cinnamomum cassia and Rhizoma coptidis) and other antidiabetic herbs, including Astragalus membranaceus, Herba Gynostemmatis, Radix Puerariae Lobatae, Folium Mori and Semen Trigonellae, is widely used to treat diabetes and has demonstrated a curative effect in the clinic, but the potential mechanism is unknown. This study aimed to explore the effects of JWJTW on diabetic rats and to clarify the underlying mechanism. METHODS: JWJTW was prepared, and the main components contained in the formula were identified by high-performance liquid chromatography (HPLC) fingerprint analysis. Diabetic rats induced by streptozotocin (STZ) and a high-sucrose-high-fat diet were treated with two concentrations of JWJTW (1.025 and 2.05 g/kg/d) for 100 days. The oral glucose tolerance test (OGTT), insulin release test (IRT) and insulin tolerance test (ITT) were performed to measure the glycometabolism of the diabetic rats at the end of the treatment period. Blood was collected to determine the serum lipid levels of the diabetic rats. Nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were detected in pancreas homogenates to analyze the oxidative stress in the pancreata of diabetic rats, and the expression levels of pancreatic and duodenal homeobox 1 (PDX-1) and insulin in the pancreas were tested by Western blot to measure pancreatic islet function. In addition, Western blots were used to measure the expression of proteins related to the insulin signaling pathway in skeletal muscle of the diabetic rats. RESULTS: The results showed that the administration of JWJTW could ameliorate impairments in glucose tolerance, insulin release function and insulin tolerance in diabetic rats. JWJTW could also dose-dependently reduce serum lipid levels in diabetic rats. JWJTW restrained oxidative stress by decreasing the expression of NO and MDA and increasing the expression of SOD and GSH-px. JWJTW improved the function of pancreatic ß cells by increasing PDX-1 and insulin expression. In addition, JWJTW restored the impaired insulin signaling; upregulated phospho-insulin receptor (pInsR) expression, insulin receptor substrate (IRS) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3K) (p85), and glucose transporter 4 (GLUT4) expression; and downregulated the serine phosphorylation of IRS. CONCLUSIONS: This study suggests that JWJTW can ameliorate type 2 diabetes by improving ß cell function and reducing insulin resistance in diabetic rats.

The effects of Jiao-Tai-Wan on sleep, inflammation and insulin resistance in obesity-resistant rats with chronic partial sleep deprivation.

BACKGROUND: Jiao-Tai-Wan (JTW), composed of Rhizome Coptidis and Cortex Cinnamomi, is a classical traditional Chinese prescription for treating insomnia. Several in vivo studies have concluded that JTW could exert its therapeutical effect in insomnia rats. However, the specific mechanism is still unclear. The present study aimed to explore the effect of JTW on sleep in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD) and to clarify its possible mechanism. METHODS: JTW was prepared and the main components contained in the granules were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The Male Sprague-Dawley (SD) rats underwent 4 h PSD by environmental noise and the treatment with low and high doses of JTW orally for 4 weeks, respectively. Then sleep structure was analyzed by electroencephalographic (EEG). Inflammation markers including high-sensitivity C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were examined in the rat plasma. Meanwhile, metabolic parameters as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (HOMA-IR) were measured. The expressions of clock gene cryptochromes (Cry1 and Cry2) and inflammation gene nuclear factor-κB (NF-κB) in peripheral blood monocyte cells (PBMC) were also determined. RESULTS: The result showed that the administration of JTW significantly increased total sleep time and total slow wave sleep (SWS) time in OR rats with PSD. Furthermore, the treatment with JTW reversed the increase in the markers of systemic inflammation and insulin resistance caused by sleep loss. These changes were also associated with the up-regulation of Cry1 mRNA and Cry 2 mRNA and the down-regulation of NF-κB mRNA expression in PBMC. CONCLUSIONS: This study suggests that JTW has the beneficial effects of improving sleep, inflammation and insulin sensitivity. The mechanism appears to be related to the modulation of circadian clock and inflammation genes expressions in PBMC.

[Research progress of berberine in treatment of diabetic kidney disease].

Diabetic kidney disease (DKD) is a chronic renal microvascular complication associated with abnormal glucose metabolism, which is an important cause of end stage renal disease. Diabetes can damage the kidney through many ways, including renal vascular, glomerular, tubular, and renal interstitial damages. Therefore, a comprehensive treatment process must be taken for the treatment of DKD, and the selection of appropriate drugs has important significance in the treatment of DKD. Berberine has significant curative effect in the treatment of DKD, and the mechanism is related to the reduction of blood sugar, improvement of renal hemodynamics abnormality, regulation of blood lipid profile and the attenuation of systemic and local inflammation.

[On Relation between Diabetes and Intestinal Flora from Theory of Pi-Wei].

Diabetes is seriously hazards to human health and its pathogeneses are not clear. Recent studies show that the imbalance of intestinal flora and the development of diabetes are closely related. Appropriate bacteria can improve blood sugar disorder. Treating diabetes from the theory of Pi-Wei is effective. Regulating intestinal flora has become a new pathway for treating diabetes from the theory of Pi-Wei. On the basis of intestinal flora, authors discussed the treatment of diabetes from Pi and Wei.

[Research progress of relationship between diabetes and intestinal epithelial tight junction barrier and intervetion of berberine].

Intestinal tight junction is an important part of the small intestinal mucosa barrier. It plays a very significant role in maintaining the intestinal mucosal permeability and integrity, preventing the bacterial endotoxin and toxic macromolecular substances into the body so as to keep a stable internal environment. Numerous studies have shown that intestinal mucosal barrier dysfunction is closely related to the development of diabetes. Therefore, protecting intestinal tight junction and maintaining the mucosal barrier have great significance in the prevention and treatment of diabetes. The effect of berberine in diabetes treatment is obvious. However, the pharmacological study found that the bioavailability of berberine is extremely low. Some scholars put forward that the major site of pharmaceutical action of berberine might be in the gut. Studies have shown that berberine could regulate the intestinal flora and intestinal hormone secretion, protect the intestinal barrier, inhibit the absorption of glucose, eliminate the intestinal inflammation and so on. Recently studies have found that the hypoglycemic effect of berberine is likely to relate with the influence on intestinal tight junction and the protection of mucosal barrier. Here is the review about the association between intestinal tight junction barrier dysfunction and diabetes, and the related hypoglycemic mechanism of berberine.

[Pharmacokinetic and pharmacodynamic characteristics of berberine and jateorhizine in Coptidis Rhizoma powder and their monomeric compounds in type 2 diabetic rats].

This article focused on a comparative analysis on the pharmacokinetic and pharmacodynamic characteristics of berberine (BER) and jateorhizine(JAT) in Coptidis Rhizoma powder (HL-P) and their monomeric compounds (BER + JAT, BJ) in type 2 diabetic (T2D) rats to explore the beneficial. effect of HL-P in the treatment of T2D. The T2D rats were treated with HL-P, BER, JAT and BJ, respectively for 63 d. The pharmacokinetic parameters, dynamic changes in blood glucose level and blood lipid values were measured. The results showed that, compared with other corresponding group, t(max), T(½ka) of BER and JAT in HL-P group were reduced, while C(max), AUC(inf), AUC(last), V(L)/F were significantly increased; compared with model group, blood glucose levels were decreased significantly in HL-P group since the 18th day, while those in BER or BJ group were reduced since the 36th day, however, blood glucose levels showed no obvious changes in JAT group; compared with model group, FFA values in all treatment group were decreased significantly. Moreover, TG, HDL and LDL value in HL-P group, LDL value in BER group and HDL value in BJ group were improved significantly. The above results showed that Coptidis Rhizoma powder showed excellent pharmacokinetic characteristics and excellent activity of lowering blood glucose and lipid. It provided a scientific basis for oral application of Coptidis Rhizoma powder in the treatment of T2D.

Effects of two genes coding squamous cell carcinoma antigen on the diagnosis and treatment of cervical squamous cell carcinoma.

OBJECTIVE: To study the effects of expressions of SCCA1 and SCCA2 in cervical squamous cell carcinoma on its diagnosis, treatment evaluation and prognosis analysis. M ethod s : Seventy-six cervical squamous cell carcinoma patients enrolled in our hospital from October 2011 to April 2013 were selected, and another 76 healthy females (without cervical tissue lesions) were enrolled as the control. SCCA1 and SCCA2 expressions in the two groups were compared by RT-PCR. The serodiagnosis results before and after chemotherapy were compared to clarify the effects of SCCA2 expression. RESULTS: The two groups had similar relative SCCA1 expression rates that were not significantly correlated with pathological factors. Before chemotherapy, the relative expression rates of SCCA2 were significantly higher in the patients with later stage (t=6.018, P=0.00082<0.05) and lymphatic metastasis (t=6.281, P=0.00192<0.05). After treatment, relative SCCA2 expression rate was decreased more significantly in the effective group than that in the ineffective group (t=10.27893, P=0.02815<0.05). CONCLUSION: The expression of SCCA1 failed to indicate the onset, diagnosis and prevention of cervical squamous cell carcinoma, whereas that of SCCA2 worked as one of the tumor markers.

[Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes].

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.