Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Research progress of microRNA in oxidative stress and lipid metabolism of non-exudative age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report / 临床耳鼻咽喉头颈外科杂志

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.

Effect of Endometriosis on Cumulus ATP, Number of Mitochondria and Oocyte Maturity in Cumulus Oocyte Complex in Mice / Efeito da endometriose no cumulus ATP, número de mitocôndrias e maturidade oocitária no complexo oocitário cumulus em camundongos

Abstract Objective Endometriosis causes a decrease in oocyte quality. However, this mechanism is not fully understood. The present study aimed to analyze the effect of endometriosis on cumulus cell adenosine triphosphate ATP level, the number of mitochondria, and the oocyte maturity level. Methods A true experimental study with a post-test only control group design on experimental animals. Thirty-two mice were divided into control and endometriosis groups. Cumulus oocyte complex (COC) was obtained from all groups. Adenosine triphosphate level on cumulus cells was examined using the Elisa technique, the number of mitochondria was evaluated with a confocal laser scanning microscope and the oocyte maturity level was evaluated with an inverted microscope. Results The ATP level of cumulus cells and the number of mitochondria in the endometriosis group increased significantly (p < 0.05; p < 0.05) while the oocyte maturity level was significantly lower (p < 0.05). There was a significant relationship between ATP level of cumulus cells and the number of mitochondrial oocyte (p < 0.01). There was no significant relationship between cumulus cell ATP level and the number of mitochondrial oocytes with oocyte maturity level (p > 0.01; p > 0.01). The ROC curve showed that the number of mitochondrial oocytes (AUC = 0.672) tended to be more accurate than cumulus cell ATP level (AUC = 0.656) in determining the oocyte maturity level. Conclusion In endometriosis model mice, the ATP level of cumulus cells and the number of mitochondrial oocytes increased while the oocyte maturity level decreased. There was a correlation between the increase in ATP level of cumulus cells and an increase in the number of mitochondrial oocytes.

The preventive effect of exogenous adenosine triphosphate on methanol-induced cardiotoxicity in rats

Abstract Exposure to methanol can cause serious consequences such as permanent visual disturbances and death. The heart tissue is highly vulnerable to ATP deficiency. Our study aimed to investigate whether exogenous ATP administration may alleviate methanol-induced ATP deficiency and subsequent oxidative damage in rat heart tissue. A total of 30 rats were divided into equal five groups; Healthy Group (HG), Methotrexate (MXG), Methanol (MeOH), Methotrexate+Methanol (MXM), and Methotrexate+Methanol+ATP (MMA) groups. We inhibited tetrahydrofolate synthesis by methotrexate to induce methanol toxicity. Methotrexate was administered to MXG, MXM, and MMA group animals for seven days with a catheter directly to the stomach at a 0,3 mg/kg dose per day. At the end of this period, % 20 methanol at a dose of 3 g/kg was administered to MeOH, MMA and MXM group animals. Immediately after methanol application, MMA group animals were injected with ATP at a 4 mg/kg dose intraperitoneally. Blood samples and heart tissues were used for biochemical analysis and histopathological examination. Co-exposure to methanol and methotrexate substantially exacerbated cardiac damage, indicating the potent cardiotoxic effects of methanol. However, the administration of exogenous ATP to MMA group animals brought biochemical oxidative damage parameters and histopathological findings closer to HG.

Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Study on the effect of polysaccharide from stigma maydison on ATP synthesis in renal mitochondria and its mechanism in D-galactose-induced aging mice / 中华老年医学杂志

Objective:To investigate the effect of Stigma Maydis Palysaccharide(SMPS)on ATP synthesis in kidney mitochondria of D-galactose-induced aging mice, and to clarify its possible mechanism.Methods:The aging mouse model was established by subcutaneous injection of D-galactose solution in the back of the neck.The 48 SPF male mice were randomly divided into normal control group(control group), D-galactose model group(D-Gal group), SMPS low-dose group and SMPS high-dose group(n=12 for each). The control group was subcutaneously injected with 150 mg/kg normal saline on the back of the neck every day, while the other three groups were subcutaneously injected with 150 mg/kg of D-gal solution on the back of the neck every day.SMPS-L and-H dose groups were given 30 mg/kg and 60 mg/kg of SMPS solution by gavage at the same day of D-Gal injection.The control group and D-GAL group were given the same volume of normal saline daily by gavage for 42 days.Blood samples were collected from the eyeball under general anesthesia after 42 days of intervention for the detection of serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px)and MDA.After harvesting the kidney tissue, various tests were used to detect ATP content, the mRNA expression levels and protein expression levels in kidney.Luciferase assay was used to detect ATP content in renal tissue.Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of succinate dehydrogenase(SDH)of complex Ⅱ, cytochrome C reductase(Cycs)of complex Ⅲ, complex Ⅳ(COXⅣ)and ATP5b in ATP synthase in mitochondrial oxidative respiratory chain.Western blot was used to detect the expression levels of mitochondrial fusion protein 2(MFN2), dynamin-related protein1(DRP1)and mitochondrial autophagy related protein P62 in renal tissues of each group.Results:Compared with control group, the activities of serum of SOD(116.53±10.01)U/mg and GSH-Px(127.58±8.74)μmol/L were significantly decreased in D-GAL group(both P< 0.01), and serum MDA content(15.42±0.91)μmol/L increased significantly in D-GAL group( P<0.01). Compared with D-GAL group, the activities of SOD(152.80±9.29)U/mg and GSH-Px(274.07±10.73)μmol/L were significantly increased in SMPS intervention group( P< 0.01), while the MDA content(8.10±0.66)μmol/L decreased significantly in SMPS intervention group( P< 0.01). Compared with control group, the content of ATP(178±4)10 -4 μmol in D-gal group was significantly decreased( P<0.01), the mRNA expression levels of SDH, Cycs and COXⅣ were not significantly changed in D-gal group, and the mRNA expression level of ATP5b(0.67±0.01)was down-regulated in D-gal group( P<0.01), the expression of MFN2 protein(0.29±0.02)was significantly decreased in D-gal group( P<0.01), and the expression of DRP1 and P62 protein(0.31±0.02 and 0.21±0.01)was significantly increased in D-gal group(both P<0.01). Compared with the D-gal group, the ATP content(193±1)10 -4 μmol in the kidney tissue of the mice was significantly increased in SMPS intervention group( P< 0.01), and the ATP5b mRNA expression and MFN2 protein expression(0.87±0.05 and 0.71±0.08)were significantly increased in SMPS intervention group(both P< 0.01), DRP1 and P62 protein expressions(0.20±0.01 and 0.10±0.01)were significantly down-regulated in in SMPS intervention group(both P< 0.01). Conclusions:SMPS can improve the mitochondrial dynamic homeostasis disorder in aging mice by increasing the activity of antioxidant enzymes, up-regulating the expression of ATP5b mRNA and MFN2 protein, down-regulating the expression of DRP1 and P62 protein, and promoting the generation of mitochondrial ATP in D-gal-induced aging mice kidney tissue.

Lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different genotypes of ATP-binding cassette subfamily B member 1 G2677T / 中华行为医学与脑科学杂志

Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.

Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia

Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC50 = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.

Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma / 中国医学科学院学报

Objective To investigate the role of ATP citrate lyase(ACLY)in the development of hepatocellular carcinoma(HCC)and the impact of this enzyme on the immune microenvironment of HCC.Methods We utilized the University of Alabama at Birmingham Cancer Data Analysis Portal and the Gene Expression Profiling Interactive Analysis to identify the changes in ACLY expression and prognosis across different tumor types from The Cancer Genome Atlas.With HCC as the disease model,we analyzed the ACLY expression in HCC samples from the gene expression database.Furthermore,we collected the clinical specimens from HCC patients to verify the mRNA and protein levels of ACLY.In addition,we conducted transcriptome sequencing after knocking down the expression of ACLY to analyze the differentially expressed genes and investigated the impact of ACLY expression interference on cell proliferation and other functions.Finally,we explored the correlations of ACLY with immune cells and immune infiltration in the tumor microenvironment,new antigens,and immune checkpoint genes.Results ACLY expression was significantly up-regulated in solid tumors including HCC(all P<0.05),and high ACLY expression was associated with overall survival rate in HCC(P=0.005).Furthermore,high ACLY expression affected the presence of immune cells(e.g.,tumor-associated fibroblasts)and the expression of genes involved in lipid metabolism(all P<0.05).Conclusions ACLY is closely related to the occurrence and development of HCC and lipid metabolism abnormalities.Moreover,it has a specific impact on the immune microenvironment of HCC.

Recent advances in poly phosphate kinase (PPK) and the construction of PPK-mediated ATP regeneration system / 生物工程学报

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.

Effect of uridine on mitochondrial function / 生物工程学报

Uridine is one of the essential nutrients in organisms. To maintain normal cell growth and intracellular metabolism, the uridine must be maintained at certain concentration. Recent studies have shown that uridine can reduce inflammatory response in organisms, participate in glycolysis, and regulate intracellular protein modification, such as glycosylation and acetylation. Furthermore, it can protect cells from hypoxic injury by reducing intracellular oxidative stress, promoting high-energy compounds synthesis. Previous studies have shown that the protective effects of uridine are closely related to its effect on mitochondria. This review summarizes the effect of uridine on mitochondrial function.

Rational design of polyphosphate kinase dual-substrate channel cavity for efficient production of glutathione by cell free catalysis / 生物工程学报

ATP is an important cofactor involved in many biocatalytic reactions that require energy input. Polyphosphate kinases (PPK) can provide energy for ATP-consuming reactions due to their cheap and readily available substrate polyphosphate. We selected ChPPK from Cytophaga hutchinsonii for substrate profiling and tolerance analysis. By molecular docking and site-directed mutagenesis, we rationally engineered the dual-substrate channel cavity of polyphosphate kinase to improve the catalytic activity of PPK. Compared with the wild type, the relative enzyme activity of the screened mutant ChPPKK81H-K103V increased by 326.7%. Meanwhile, the double mutation expanded the substrate utilization range and tolerance of ChPPK, and improved its heat and alkali resistance. Subsequently, we coupled the glutathione bifunctional enzyme GshAB and ChPPKK81H-K103V based on this ATP regeneration system, and glutathione was produced by cell-free catalysis upon disruption of cells. This system produced (25.4±1.9) mmol/L glutathione in 6 h upon addition of 5 mmol/L ATP. Compared with the system before mutation, glutathione production was increased by 41.9%. After optimizing the buffer, bacterial mass and feeding time of this system, (45.2±1.8) mmol/L glutathione was produced in 6 h and the conversion rate of the substrate l-cysteine was 90.4%. Increasing the ability of ChPPK enzyme to produce ATP can effectively enhance the conversion rate of substrate and reduce the catalytic cost, achieving high yield, high conversion rate and high economic value for glutathione production by cell-free catalysis. This study provides a green and efficient ATP regeneration system that may further power the ATP-consuming biocatalytic reaction platform.

Study of glycine solution in preparation of frozen thawed deglycerolized erythrocytes / 中国输血杂志

【Objective】 To study the protective effect of glycine solution on frozen red blood cell thawing process. 【Methods】 A total of 20 bags of 1 U of leukocytes reduced suspended red blood cells within 6 days were selected for the study. After mixing, each 2 bags of suspended red blood cells were divided into 2 bags and into two groups with 10 bags of 1 U in each group, and were frozen for storage. One group was deglycerolized with sodium chloride solution (control group), and one group was deglycerolized with glycine solution (experimental group). The hemoglobin, free hemoglobin, residual glycerol, total glycerol in red blood cells, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were detected in the two groups. 【Results】 Compared with the free hemoglobin content (0.90±0.05)g/L and residual glycerol content (1.17± 0.08)g/L in the control group, the final product red blood cell supernatant free hemoglobin content (0.77±0.15)g/L and residual glycerol content (0.79±0.33)g/L in the experimental group were decreased, and the difference was statistically significant (P<0.05). Compared with the ATP content (4.03±0.38)µmol/gHb and 2,3-DPG content (485.65±78.08)µg/L in the control group, the ATP content (4.41±0.35)µmol/gHb and 2,3-DPG content (656.28±116.68)µ g/L in the experimental group were significantly increased, with statistical significance (P<0.05). 【Conclusion】 Using glycine solution instead of sodium chloride solution to prepare frozen thawed deglycerolized erythrocytes achieved the effect of protecting erythrocytes, reduced the hemolysis rate of erythrocytes and glycerin residue, and increased the recovery rate of erythrocytes.

Rapid determination of microbial contamination of Bupleurum chinense DC. decoction slices by ATP bioluminescence technology combined with statistical analysis methods / 药学学报

This study focuses on the microbial quality control of the Chinese herbal decoction pieces. In view of the shortcomings of traditional culture methods such as slow detection speed and inability to detect unculturable microorganisms, a new method based on ATP bioluminescence technology combined with statistical analysis methods was established to rapidly predict and quantitatively detect the total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) contaminated Bupleurum chinense DC. decoction pieces. Based on the optimized ATP bioluminesence detection system, accurate detection of pure bacterial solution of Escherichia coli, Bacillus subtilis and Staphylococcus aureus can be achieved, with detection limits of 47.86, 89.13 and 1 862.09 CFU·mL-1, respectively. The detection time was 6.5 h, and the detection cost was as low as 2 yuan/time. The upper and lower warning limits of TAMC were determined by the misjudgment rates of 10% and 20%, respectively. And the warning limit of TYMC was determined by the misjudgment rate of 20%. The proposed crossing method could quickly predict the amount of microbial contamination in Bupleurum chinense DC. decoction pieces. The constructed partial least squares regression (PLSR) model could accurately quantify the quantity of microbial contamination in Bupleurum chinense DC. decoction pieces. The optimal PLSR prediction model for TAMC had a correction coefficient (R2) of 0.826, a root mean square error of correction set (RMSEE) of 0.468 and a root mean square error of cross-validation set (RMSECV) of 0.465. The R2, RMSEE and RMSECV in the prediction model of TYMC were 0.778, 0.543 and 0.541, respectively. The aim of this study is to establish a kind of rapid detection method and prediction models for the microbial limit of traditional Chinese medicine and Chinese herbal decoction pieces, and to provide a more convenient and sensitive detection technology for the microbial quality process control of traditional Chinese medicine products.

Peptide P3 ameliorates foam cell formation in RAW264.7 cells and its molecular mechanisms / 中国药理学通报

Aim To examine the effect of peptide P3 on lipid accumulation in RAW264.7 cells and the underlying molecular mechanism. Methods MTT method was used to screen the concentration of peptide P3 and oxidized low density lipoprotein(ox-LDL),and RAW.264.7 cells were induced to form foam cells by ox-LDL with 80 mg·L

Función biológica de AMPK- ß2 en músculo esquelético y su dinámica estructural después de la activación por SC4 / Biological role of AMPK- ß2 in skeletal muscle and its structural dynamics after activation by SC4

INTRODUCCIÓN: la Proteína Quinasa Activada por AMP (AMPK), es una enzima monitora y reguladora central del estado energético celular, por tanto, es responsable de la respuesta celular al suministro y demanda de energía. El AMP actúa como activador en condiciones de déficit energético, mientras que el ATP la inactiva cuando las condiciones energéticas son más favorables. Debido a su función central en el metabolismo, la AMPK surge como un blanco proteico prometedor para el tratamiento de diferentes enfermedades como la Diabetes Mellitus tipo 2 (DM2), Síndrome Metabólico (SM), Cáncer, entre otros. Existen múltiples isoformas de AMPK que se regulan y expresan diferencialmente en todo el organismo. La isoforma AMPK­ß2 se expresa casi exclusivamente en músculo esquelético y dado que este es el órgano primario para el almacenamiento y eliminación de Glucosa, AMPK­ß2 puede dirigir su homeostasis por una ruta independiente a la Insulina. La molécula activadora SC4 tiene una gran selectividad por AMPK­ß2 y debido a su función biológica, podría servir como modelo farmacológico para coadyuvar el tratamiento de enfermedades metabólicas. OBJETIVO: análisis de la dinámica molecular de activación de la AMPK­ß2. METODOLOGÍA: en el presente estudio, se emplean herramientas bioinformáticas como Chimera 1.15 y Phyton Molecular Viewer. RESULTADOS: el análisis in silico permitió comprender varios aspectos estructurales relacionados con la acción de SC4 sobre la estructura trimérica de la AMPK, los aminoácidos con los que interacciona y cómo su estructura química le otorga gran selectividad. También fue útil para en un futuro, ampliar los criterios de extracción, identificación y/o diseño de compuestos activos a partir de fuentes naturales, con propiedades funcionales similares o aún mejores a SC4, para así poder emplearlos con un enfoque terapéutico que beneficie a nuestra población.

INTRODUCTION: protein Kinase Activated by AMP (AMPK), is a monitor enzyme and a central regulator of the energetic cellular state, therefore, it is responsible for the cellular response to the supply and demand of energy. AMP acts as an activator in conditions of energy deficit, while ATP inactivates it when energy conditions are more favorable. Due to its central role in metabolism, AMPK appears as a promising protein target for the treatment of different diseases such as Diabetes Mellitus type 2 (DM2), Metabolic Syndrome (SM), and Cancer among others. There are multiple isoforms of AMPK that are regulated and differentially expressed throughout the body. The ß2-AMPK isoform is expressed almost exclusively in skeletal muscle and since this is the primary organ for Glucose disposal and storage, ß2-AMPK has an established role as a driver of insulin-independent Glucose clearance. The activator SC4 has a high selectivity for ß2-AMPK and due to its biological function; it could serve as a pharmacological model to aid the treatment of metabolic diseases. OBJETIVE: to analize the molecular dinamic of AMPK- ß2 activation. METHODOLOGY: in the present work we employed bioinformatics, Chimera 1.15 and Phyton Molecular Viewer. RESULTS: the in silico analysis allow us to understand many many structural features related to the action of SC4 on the trimeric structure of AMPK, the specific amino acids involved in the interaction and how its chemical structure gives it high selectivity. Thus, this structural analysis will be useful in order to broaden the criteria for extraction, identification and/or design of active compounds from natural sources, with similar or even better properties than SC4, to use them in a future, with a therapeutic approach that benefits our population.

A STUDY TO EVALUATE THE IMPORTANCE OF FASTING LIPID PROFILE ESTIMATION AS THE PART OF INITIAL EVALUATION OF HIV POSITIVE PATIENTS BEFORE STARTING HAART

BACKGROUND:-There is evidence that ART is associated with lipodystrophy syndrome, a disturbance of lipid metabolism characterised by insulin resistance, dyslipidaemia, and fat maldistribution, metabolic bone disease (osteopenia and/or osteoporosis), and lactic acidosis. ART- associated dyslipidaemia is characterized by elevated serum concentrations of total cholesterol, triglycerides, low density lipoprotein 2(LDL-c), very low-density lipoprotein (VLDL), and Apo lipoprotein B (apoB) and low levels of high density lipoprotein (HDL-c) constituting an atherogenic lipid 1pro?le . In this study 143 young patients who were attending the Antiretroviral Therapy Plus MATERIAL AND METHODS:- Centre & Medicine Wards, ACSR GMC NELLORE were included randomly. 5ml Sample preparation and Biochemical assay :- of venous blood sample was collected by venipuncture from 12 hours overnight fast and centrifuged at 3000 cycles per minute and serum was separated for lipid pro?le measurement within one hour of blood collection. The serum levels of TC, HDL-C, LDL-C, VLDL and TG were measured using AU480 BECKMANS random access fully automated auto analyzer at Biochemistry laboratory, ACSR GMC, NELLORE. TC, LDL and TC/HDL lipid pro?les are signi?cant. F-Signi?cant values are RESULTS;- <0.05, reject null hypothesis. It means that the difference among the lipid pro?les of TC, LDL and TC/HDL in the study group is statistically signi?cant with respect to regimen groups. HDL, TG and VLDL lipid pro?les are not signi?cant. F-Signi?cant values are >0.05, no evidence to reject null hypothesis. It means that the no signi?cant difference among the lipid pro?les of HDL, TG, and VLDL in the study group is not statistically signi?cant with respect to regimen groups. Signi?cant CONCLUSIONS:- metabolic and morphological alterations occur in HIV infected patients especially in patients on HAART. The patients on HAART had an elevated Castelli Index I, indicating an increased risk for atherosclerotic cardiovascular disease in this population. There is need to assess lipid pro?les at baseline before initiation of HAART treatment and lipid pro?le monitoring during therapy to monitor any rising trends. New medications with more lipid friendly pro?les within existing drugs such as darunavir (PI), etravirine (NNRTI), new classes of drugs such as integrase inhibitors (raltegravir) and CCR5 inhibitors (maraviroc) can be used to avoid dyslipidaemia

Analysing The Correlation Of Lipid Profile Pattern In Chronic Rheumatic Heart Disease (RHD) Patients

Background:The global burden of ARF and RHD is significant, and is predominantly found in populations living in low-resource settings. This study was conducted with a view for analysing the lipid profile variation in patients with chronic Rheumatic Heart Disease (RHD) and correlating the same. The early management of RHD has to be started to prevent further cardiac complications. To date no hypothesis is established on the relation between the Lipid Profile and RHD. This study would be beneficial to Indian cardiologists in defining the optimal treatment by the choice of antibiotic therapy and Lipid lowering agents like Statins.Material And Methods:It was a cross-sectional study carried out on the patients visiting Cardiology Out Patient Department (OPD) at a tertiary care hospital in Ahmedabad and who were diagnosed with Rheumatic Heart Disease (RHD).The blood lipids levels of thepatients were evaluated with current classification schemes and treatment levels for hyperlipidemia based on the National Cholesterol Education Panel’s (NCEP) Adult Treatment Program-3 (ATP-III) guidelines.Result:Total 89 patients were included in the study. 76 patients were associated with dyslipidaemia and 13 patients had normal lipid values. As far as total cholesterol levels were concerned, 23 out of 76 patients (30.26%) had above target levels for total cholesterol. Also 46 patients out of 76(60.52%) had raised triglycerides levels and 47 patients (61.84%) had raised LDL levels. As far as HDL levels were concerned, 38 out of 76 patients (50.00%) had below desirable levels. The frequency of deranged LDL is higher as compared to HDL, triglycerides and total cholesterol levels. If these values are to be co-related to the disease, then LDL as a lipid parameter stands most significant.Conclusion:Morbidity and mortality in RHD is very high in Indian patients and one of the determinants of the cardiovascular morbidity is the increased lipid levels. The frequency of deranged LDL is higher as compared to HDL and total cholesterol levels in these patients. This study was planned to evaluate an entirely novel hypothesis that RHD is an independent risk factor for Atherosclerosis and CAD. The exact reason behind the occurrence is unknown but it can be environmental or genetic. RHD and Dyslipidaemia might engulf younger patients. The study is also aimed at evaluating all lipid parameters with RHD.