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Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

The study focused on changes or cut-offs of glycaemia, insulin resistance and body mass index within the C-peptide reference range (260-1730 pmol/l). The metabolic profile of individuals in the Czech Republic without diabetes (n = 3186) was classified by whiskers and quartiles of C-peptide into four groups with the following ranges: 290-510 (n = 694), 511-710 (n = 780), 711-950 (n = 720) and 951-1560 pmol/l (n = 673). Fasting levels of glucose, insulin, HOMA IR (Homeostasis Model Assessment for Insulin Resistance) and BMI (body mass index) were compared by a relevant C-peptide range. Participants taking medication to control glycaemia were excluded. The evaluation involved correlations between C-peptides and the above parameters, F-test and t-test. Changes in glucose levels (from 5.3 to 5.6 mmol/l) between the groups were lower in comparison to insulin, which reached relatively greater changes (from 4.0 to 14.2 mIU/l). HOMA IR increased considerably with growing C-peptide concentrations (0.9, 1.5, 2.2 and 3.5) and BMI values showed a similar trend (28.3, 31.0, 33.6 and 37.4). Considerable changes were observed for insulin (5.2 mIU/l, 57.8%) and HOMA IR (1.3, 61.3%) between groups with C-peptide ranges of 711-950 and 951-1560 pmol/l. Although correlations involving C-peptide, insulin, glucose and BMI seemed to be non-significant (up to rxy = 0.25), the mean values of insulin, HOMA IR and BMI showed statistically significant changes between all groups with various C-peptide concentrations (p ≤ 0.001). Generally, most important differences appeared in glucose metabolism and body mass index between C-peptide ranges of 711-950 and 951-1560 pmol/l. Absolute and relative changes of C-peptide concentrations are possible to use for the assessment of glucose regulatory mechanism. The spectrum of investigated parameters could be a useful tool to prevent the risks linked with the alterations of glycaemia.

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function.

The study focused on the changes in C-peptide, glycemia, insulin concentration, and insulin resistance according to LDL-cholesterol concentration ranges. The metabolic profile of individuals in the Czech Republic (n = 1840) was classified by quartiles of LDL-cholesterol into four groups with the following ranges: 0.46-2.45 (n = 445), 2.46-3.00 (n = 474), 3.01-3.59 (n = 459), and 3.60-7.18 mmol/l (n = 462). The level of glucose, C-peptide, insulin, and area of parameters during OGTT and HOMA IR were compared with a relevant LDL-cholesterol range. The evaluation involved correlations between LDL-cholesterol and the above parameters, F-test and t-test. Generally, mean values of glucose homeostasis-related parameters were higher with increasing LDL-cholesterol levels, except for mean HOMA IR values which rapidly increased (2.7-3.4) between LDL-cholesterol ranges of 3.00-3.59 and 3.60-7.18 mmol/l. Glucose, C-peptide, insulin concentrations, and the area of parameters reached greater changes especially after glucose load during OGTT (p ≤ 0.001). Considerable changes were already observed for the above parameters between groups with LDL-cholesterol ranges of 2.46-3.00 and 3.01-3.59 mmol/l. HOMA IR increased with higher LDL-cholesterol concentrations, but the differences in mean values were not statistically significant. Most important differences appeared in glucose metabolism at LDL-cholesterol concentrations of 3.60-7.18 mmol/l in comparison to LDL-cholesterol lower ranges. In particular, the areas of C-peptide, glucose, and insulin ranges showed statistically significant differences between all groups with growing LDL-cholesterol ranges. The variances of HOMA IR statistically differed between groups created according to LDL-cholesterol concentrations ranges.

Backgrounds: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. Methods: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. Results: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. Conclusions: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.

Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

A substantial threat to worldwide health, the proliferation of antibiotic-resistant bacteria compels researchers to seek innovative antibacterial substances. This systematic review assesses the role of nanoparticles, particularly Calcium oxide and Silicon oxide nanoparticles, in infection control. The article examines the mechanisms by which these nanoparticles act against various bacteria and evaluates their potential as novel agents in infection control strategies. A systematic literature search from 2015 to 2024 encompassing Web of Science, PubMed, Wiley, Science Direct, and Google Scholar, yielded 70 publications meeting the review criteria. This comprehensive methodology provides a thorough understanding of the capabilities and limitations of Calcium oxide and Silicon oxide nanoparticles as antibacterial agents. The review aims to build a solid foundation for the utilization of nanoparticles in addressing the obstacles presented by antibiotic resistance by combining data from various investigations. Additionally, it aims to explore the safety and environmental implications associated with their use in clinical and environmental settings, providing a comprehensive analysis that may contribute to future studies and real-world applications in the field of antimicrobial technology.

Pseuduvaria macrophylla (Family: Annonaceae) is commonly used as medicinal plant in Malaysia. A recent study with the Pseuduvaria species showed antioxidant and antidiabetic effects. This study aimed to ascertain antidiabetic potential of methanolic extract of Pseuduvaria macrophylla bark (PM) using streptozotocin-nicotinamide induced diabetic rat models. Various phytochemical and biochemical properties of the plant have been evaluated. The results showed that the extract has potentially normalized the elevated blood glucose levels by upregulating the insulin and C-peptide levels and alleviated oxidative stress by improving glutathione (GSH) and reducing lipid peroxidation (LPO) in the diabetic rats. In addition, PM has drastically downregulated the levels of pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathological examination of the pancreas in PM treated diabetic rats showed significant recovery of the pancreatic structural degeneration and thus reflected the protective role of PM against peroxidation damage by a rise in insulin level as evidenced by the immunohistochemistry study. The improved expressions of GLUT-1, GLUT-2 and GLUT-4 further confirmed the restoration of β-cell mass by PM. Interestingly, the findings demonstrated the antioxidant, anti-inflammatory and antihyperglycemic potential of PM which may provide future lead for the management of type-2 diabetes.

Thirty-one of sixty dyspeptic patients tested positive for Helicobacter pylori colonization in this study, as determined by histopathology and 16S rRNA. The cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes were found in 67.7 and 93.5% of H. pylori patients, respectively. The cagA gene was found to be associated with 100% of patients with duodenal erosion and ulceration identified via endoscopy examination. In addition, 86.7% of patients with cancerous and precancerous lesions, glandular atrophy, and intestinal metaplasia identified via histopathology examination. The vacA s1m1 mutation was associated with more severe forms of gastric erosion and ulceration, as well as the presence of precancerous and cancerous lesions. Eighteen (64.3%) of the twenty-eight isolates were classified as multi-drug resistant (MDR) or pan-drug resistant (PDR) H. pylori. Due to a resurgence of interest in alternative therapies derived from plants as a result of H. pylori resistance to the majority of commonly used antibiotics, the inhibitory activity of five essential oils extracted from some commonly used medicinal plants was evaluated in vitro against drug-resistant H. pylori clinical isolates. Cinnamomum zeylanicum essential oil demonstrated the highest anti-H. pylori activity when compared to the other essential oils tested. Cinnamaldehyde was the most abundant compound in C. zeylanicum (65.91%). The toxicological evaluation established the safety of C. zeylanicum oil for human use. As a result, C. zeylanicum essential oil may represent a novel antibacterial agent capable of combating drug-resistant H. pylori carrying cytotoxin genes.

Background: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats. Methods: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated. Results: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group. Conclusions: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.

Background: Dysmetabolic iron overload syndrome (DIOS) is characterized by hyperferritinemia and normal transferrin saturation level with components of metabolic syndrome (MS). Among cases of MS, we determined those with DIOS and their characterizations, then we evaluated the association between plasma catecholamines status and hypertension in DIOS. Methods: We compared 101 hypertensive patients with 50 healthy participants (control group). Iron (iron, transferrin, and ferritin), insulin, and plasma catecholamine (adrenaline, noradrenaline, and dopamine), profiles were measured for both groups. Homeostasis model assessment of insulin resistance index and transferrin saturation were also calculated. Results: Out of 101 hypertensive patients, 64 were diagnosed with MS, and 6 of the latter met the DIOS diagnostic criteria. Significantly, DIOS patients were older and had lower body mass index (BMI) compared with hypertensive non-DIOS patients with p-values of (0.026), and (0.033), respectively. Adrenaline, noradrenaline, and dopamine levels did not differ significantly between DIOS and non-DIOS patients. Conclusions: Of the MS patients, 9.3% were diagnosed with DIOS. Accordingly, complete iron profiling should be performed routinely in the cases of MS for early diagnosis of DIOS, to prevent future complications. Further studies are required to test the hypothesis linking older age and lower BMI with the pathogenesis of DIOS.

Background: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico. Methods: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity. Conclusions: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.

The purpose of this study was to determine the changes in the resting level of serum cortisol, testosterone and T/C ratio in response to different training modalities and their variations. A secondary purpose was to identify if the various six weeks training programs are an effective way to improve physical fitness. 86 regularly active young males were assigned to one of six groups: Endurance constant running (ECR), Endurance interval running (EIR), Resistance training (RT), Explosive training (ET), Speed-endurance 50 m running (SER50) and Speed-endurance 150 m running (SER150) training. The resting levels of testosterone, cortisol and T/C ratio, as well as physical fitness, were measured. The ECR, EIR, and RT training program decreased COR level (P < 0.05). An increase of the T/C ratio was observed in the ECR and EIR group (P < 0.05). Except for SER50, each training program improved physical fitness. Our results suggest that endurance and resistance training modalities performed with a moderate to vigorous intensity may be a usable way to manage the resting cortisol level and enhance physical fitness in active young males.

In this study, the therapeutic efficacy of bergenin was examined against high-fat diet (HFD) induced type 2 diabetes in C57BL/6J mice. These mice were fed continuously HFD for 16 weeks and subjected to intragastric administration of various doses (10, 20 and 40 mg/kg body weight (BW)) of bergenin daily for subsequent 8 weeks. Bergenin supplementation to HFD-fed mice lower body weight gain, plasma glucose and insulin in diabetic mice. It further restored the alterations of biochemical parameters to near normal levels in diabetic mice. As compared to other two doses of 10 mg and 20 mg, bergenin 40 mg/kg BW were showed significant protective effect on the biochemical parameter studied. Consequently, it improved insulin-dependent glucose transport in the liver through translocation and activation of glucose transporter protein 2 (GLUT 2) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (AKT) dependent pathway. These findings provided evidence to exhibit that bergenin could improve liver tissue hyperglycemia, insulin sensitivity increase glucose uptake and shows hepatoprotective. Hence it might be used in the management of obesity-associated type 2 diabetes mellitus.

The relationship between glycaemia and lipoprotein metabolism has not been completely clarified, and slight differences may be found between local authors, trials and evaluated parameters. Therefore this cross-sectional study investigated fasting cholesterol and glucose levels along with the determination of atherogenic index in a cohort of healthy individuals from the Czech Republic in relation to their fasting C-peptide levels. Data were collected between 2009 and 2018 and a total of 3189 individuals were stratified by C-peptide reference range (260-1730 pmol/l) into three groups - below (n = 111), within (n = 2952) and above (n = 126). Total, HDL, LDL cholesterol and atherogenic index were used to compare lipoprotein levels by relevant C-peptide concentrations. Participants using the supplements to affect lipid or glycaemia metabolism were excluded from this study. The evaluation of blood parameters in a fasting state included correlations between C-peptide and cholesterols, differences of variances (F-test) and the comparison of lipoprotein mean values (t-test) between the groups created by the C-peptide reference range. Mean values of total (4.9, 5.1, 5.3 mmol/l), LDL (2.6, 3.1, 3.4 mmol/l) cholesterol and atherogenic index (2.1, 2.8, 3.7) were higher with increasing C-peptide levels, whereas HDL was inversely associated with fasting C-peptide concentration. A positive and negative correlation between atherogenic index (rxy = 0.36) and HDL level (rxy = -0.36) with C-peptide values was found. Differences of HDL, LDL and atherogenic index were, in particular, recorded between the groups below and above the reference range of C-peptide (p ≤ 0.001). Considerable differences (p ≤ 0.001) were also observed for the same lipoprotein characteristics between the groups above and within the C-peptide reference. Generally, the type of cholesterol is crucial for the evaluation of specific changes concerning the C-peptide range. Lipoprotein concentrations differ in relation to C-peptide - not only below and above the physiological range, but also inside and outside of it. Conclusions: Fasting levels of cholesterol, plasma glucose, and atherogenic index were strongly associated with fasting C-peptide levels in healthy individuals. Our data suggest that fasting C-peptide could serve as a biomarker for the early detection of metabolic syndrome and/or insulin resistance prior to the manifestation of type 2 diabetes.

This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.

Objective: The role of Helicobacter pylori (Hp) in the pathological processes of the gastric mucosa is well understood. Decreasing trend in successful eradication of HP from the stomach was observed in last years. This lack of succes is mainly caused by increasing ATB resistance. Nevertheless other possible causes of this phenomenon are being explored. Thus, many studies have focused on the search for extragastric reservoirs as potential sources of persistence or reinfection after successful Hp eradication. The pathological potential of Hp at these localities has also been studied. Methods: Our study aimed to determine the presence of Hp inside the salivary glands ductal system through its detection from sialolites. Subsequently, we tried to prove the possible ability of Hp to penetrate the salivary gland parenchyma by detecting Hp from the tissue of salivary tumors. Concrements and salivary tumor tissue samples were collected using sialendoscopy or standard surgery, and Hp detection and genotyping were performed through PCR. Results: Hp was detected in 68.3% of the sialopathy samples. VacA S1AM1 was the most common genotype. CagA-positive genotype represented only 34% of the total number of positive samples. Conclusion: Our findings of Hp positivity in concrements provide compelling evidence of Hp presence in the ductal system of salivary glands. Confirmation of Hp presence in tumor tissue suggests its potential ability to infiltrate the gland's parenchyma. Further research is needed to confirm Hp's ability to cause local infection, as well as the possible causal association between Hp presence in the studied region, sialolithiasis, and salivary gland tumors.

The potency of one reversible inhibitor of acetylcholinesterase (6-chlorotacrine), one reactivator of acetycholinesterase (K027) and their combination to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated. While 6-chlorotacrine was able to markedly protect mice against acute toxicity of soman and the pharmacological pretreatment with 6-chlorotacrine increased the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice more than two times, the bispyridinium oxime K027 did not protect mice from acute toxicity of soman, however, the pharmacological pretreatment with this compound was able to markedly increase the efficacy of antidotal treatment of soman-poisoned mice. On the other hand, the combination of both modulators of acetylcholinesterase did not increase the prophylactic efficacy of 6-chlorotacrine alone. These findings demonstrate that pharmacological pretreatment of soman-poisoned mice can be promising and useful in the case of administration of 6-chlorotacrine while the administration of the oxime K027 did not bring any additional benefit when combined with 6-chlorotacrine.

Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.

Open wounds are easily susceptible to infection by multi-drug resistant (MDR) pathogens. The emergence of MDR super bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus spp, fungi such as Aspergillus niger and Candida spp, has been identified to significantly increase the incidence rate. Therefore, it is necessary to develop a suitable barrier to prevent infection and enhance wound healing. On the other hand, medicinal plants could represent a significant source of new antimicrobial drugs for combating MDR pathogens. Out of 60 clinical skin burn cases, 51 patients (85%) had polymicrobial infections, while the remaining had monomicrobial infections. Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia were identified as the most common bacterial isolates based on morphological and biochemical tests. However, Candida albicans, Candida parasitosis, Candida glabrata, Candida famata, Aspergillus niger, and Exophilia spinifera were the most common fungal isolates found in skin burn cases. MDR classification was reported in 21 of the 39 bacterial isolates and 8 of the 27 fungal isolates. The antimicrobial activity of tested acetonic plant extracts rosemary, henna, and licorice against MDR isolates was compared to the commercial antibiotic agents. Acetonic rosemary extract outperformed henna and licorice extracts in antibacterial activity, while licorice extract outperformed henna and rosemary extracts on antifungal activity. As a result, rosemary and licorice extracts were chosen to prepare a topical cream for further in vivo wound healing and histopathology. Based on the antimicrobial potential of acetonic plant extracts against MDR isolates, BI-41 and FI-17 were chosen for in vivo wound healing. BI-41 stands for the molecularly identified species Pseudomonas aeruginosa SSM-15, while FI-17 stands for molecularly identified species Aspergillus niger SSM-27. In vivo testing showed that both cream formulas had excellent healing properties when administered topically. In vivo histopathological examination revealed that acetonic rosemary and licorice extract could be promising for wound healing, combating MDR pathogens of burn wound infections.

This study was designed to investigate effects of insulin on fracture healing and expression of vascular endothelial growth factor (VEGF) in diabetic rats. Wister rats were randomly divided into diabetic control (n=66), diabetic insulin (=66) and non-diabetic control group (n=66). Diabetes was established by peritoneal injection of alloxan. Tibia fracture was surgically created and was allowed to heal. Radiological and biomechanical examinations were performed on the healing tibia. Immuohistochemistry was used to assess VEGF expression in the healing fracture tissues. Cortical reconstruction of the fracture sites in non-diabetic control and diabetic insulin groups was more rapid than in diabetic control group within 6 weeks of the fracture. Mechanical strength of the affected tibia in the diabetic insulin and non-diabetic control group was superior to diabetic control group. Histological examination of the fracture sites revealed a delay in chondrocyte maturation and hypertrophy in diabetic control group. VEGF expression was widely distributed in fracture sites within the first 4 weeks in control and diabetic insulin treatment group. However VEGF expression in the callus and periosteum in diabetic control group was much less than in diabetic insulin or non-diabetic control group. In conclusion, diabetes delays fracture healing and adversely affects callus formation with a reduced VEGF expression at the fracture sites. Insulin therapy improves fracture healing in diabetes rats, possibly through enhancing VEGF expression in the fractured bones.

Context and objective: Zerumbone has been reported to exert anti-microbial effects, but the mechanism by which the compound exerts its action is not known. Thus, this study aimed to investigate the mechanism of action of zerumbone against methicillin-resistance Staphylococcus aureus (MRSA), using the atomic force microscopy (AFM), scanning electron microscopy (SEM), and flow cytometry techniques. Methods: MRSA (NCTC 13277) cell viability was determined using the microplate AlamarBlue assay. AFM and SEM were used to determine the morphology of zerumbone-treated MRSA cells. Flow cytometric analysis was used to determine the effect of zerumbone on bacterial membrane permeability and membrane potential, using the propidium iodide (PI) staining method, membrane potential-sensitive fluorescence probe, and DiBAC4(3) dye. DCFDA dye was used to determine the generation of reactive oxygen species (ROS) by MRSA. Results: Zerumbone significantly inhibited MRSA growth with a minimum inhibitory concentration (MIC) of 125 µg/ml. The AFM analysis showed that zerumbone caused leakage of cytoplasmic content from the bacterial cells. Ultrastructure analysis showed small colonies of the bacteria with pores on the membrane surface. There were increases in zerumbone-treated MRSA PI and DiBAC4(3) fluorescence, indicating an increase in cell membrane permeability and a decrease in membrane potential that culminated in the loss of membrane structural integrity and bacterial death. Based on DCFDA dye analysis, zerumbone also reduced ROS production by MRSA. Conclusions: Zerumbone exerts anti-MRSA effects by causing membrane depolarization, increasing membrane permeability, and finally disrupting cell membrane and bacterial killing.

Amyloidosis is a group of diseases caused by the accumulation of insoluble protein aggregates in different parts of the body. Repeated subcutaneous injection of insulin hormones in diabetic patients leads to localized amyloidosis that is found to be cytotoxic. Thus, agents that can dissociate these aggregates are critically needed. In the present study, insulin amyloid dissociation was demonstrated by the treatment of an enzyme lumbrokinase (LK) isolated from earthworm. Thioflavin T (ThT) fluorescence, solution turbidity, particle size analysis, FTIR, CD, atomic force microscopy and cell viability assay were employed to support the dissociation of insulin amyloid in vitro. The small animal optical imaging was used to explore the dissociation of amyloid fibrils in vivo using zebrafish model. The activity of LK towards amyloid dissociation was compared with the standard amyloid fibril degrading agent nattokinase (NK). Our results indicated that LK can be a probable fibril degrading agent for the dissociation of amyloids.

Infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacter cloacae are considered as major therapeutic challenge due to their multidrug-resistant (MDR) phenotype against conventional antibiotics. WLBU2 is an engineered cationic peptide with potent antimicrobial activity. This in-vitro study aimed to evaluate the effects of WLBU2 against clinical isolates of the aforementioned bacteria and assess whether synergistic effects can be achieved upon combination with conventional antibiotics. The minimum inhibitory concentrations (MICs) of antimicrobial agents against bacterial clinical isolates (n = 30/strain) were determined using the microbroth dilution assay. The minimum bactericidal concentrations (MBCs) of WLBU2 were determined from microbroth dilution (MICs) tests by subculturing to agar plates. MICs of WLBU2 were evaluated in the presence of physiological concentrations of salts including NaCl, CaCl2 and MgCl2. To identify bacterial resistance profile, MRSA were treated with Oxacillin, Erythromycin and Vancomycin, while Ceftazidime, Ceftriaxone, Ciprofloxacin and Imipenem were used against Enterobacter cloacae. Combination treatments of antibiotics and sub-inhibitory concentrations of WLBU2 were conducted when MICs indicated intermediate/resistant susceptibility. The MICs/MBCs of WLBU2 were identical for each respective bacteria with values of 0.78-6.25 μM and 1.5-12.5 μM against MRSA and Enterobacter cloacae, respectively. WLBU2 was found as salt resistant. Combination treatment showed that synergistic and additive effects were achieved in many isolates of MRSA and Enterobacter cloacae. Our data revealed that WLBU2 is a potent peptide with bactericidal activity. In addition, it demonstrated the selective advantage of WLBU2 as a potential therapeutic agent under physiological solutions. Our findings also support the combination of WLBU2 and conventional antibiotics with potential application for treatment of resistant bacteria.

The aqueous extract of Cichorium intybus (CIE) leaves have shown the properties of protecting against pancreatic β-cell damage by streptozotocin (STZ), but the molecular mechanisms of its protection are not completely elucidated yet. Our current study focuses on elucidating the mechanisms of these preventive effects of CIE in MIN6 cells and an in-vivo model of Wistar rats. CIE offers protection against STZ in MIN6 cells by reducing the pro-oxidants and increasing the activity of the antioxidant enzymes. In vitro results also indicated that CIE inhibited cytotoxicity, reduced Reactive oxygen species (ROS), maintained glucose-stimulated insulin secretion and reduced NF-κB p65 translocation into the nucleus. The group administered with a 250 mg/kg dose of CIE in vivo has shown an ability to maintain blood glucose level and also to preserve the number and morphology of pancreatic islets when compared to the diabetic group treated with STZ. Probably, active compounds like quercetin, rutin, and catechin present in CIE, preserve the integrity of pancreatic islets thereby protecting β-cells from the adverse effects of STZ.

Chronic infections caused by Pseudomonas aeruginosa (P. aeruginosa) isolates are mainly related to resistance to antimicrobials and the production of certain virulence factors. The purpose of this study was twofold: to investigate the prevalence of virulence genes and to study the relationship between biofilm formation/alginate production/antibiotic resistance and the presence of genes associated with biofilm, alginate, flagella and exotoxin A in clinical isolates of P. aeruginosa.
Microtiter plate biofilm assay and Carbazole method were used to examine the biofilm formation and alginate production ability of the isolates, respectively. The genes, ppyR, pslA, pelA (biofilm formation), algD, algU, algL (alginate production), fliC (flagella) and exoA (exotoxin A) were detected by PCR.
Biofilm formation as well as alginate production ability was found in 47.1% of the clinical isolates. Based on PCR data, the frequency distribution of the genes in the clinical isolates was as follows: ppyR (99%), pslA (83.7%), pelA (45.2%), algU (90.4%), algL (73.1%), algD (87.5%), exoA (84.6%) and fliC (70.2%). Biofilm formation ability of the isolates was significantly correlated with the presence of the genes, pelA and fliC (statistically significant). In addition, 58.65% of the isolates were resistant to three or more different classes of antibiotics.

Background and aim
Diabetes mellitus is a very common metabolic disease with a rising incidence. It is one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. Adipocytokines, synthetized by adipose tissue influence metabolic pathways and disorders in various ways. In this review article, we chose the most researched adipocytokines and evaluated their relationship to posttransplant diabetes mellitus. The aim of this paper is to summarize current knowledge and discuss their perspective role in diagnostics or therapy of the new onset diabetes mellitus after transplantation.

Plants offer unlimited source of bioactive compounds that have tremendous applications in pharmaceutical industry. To find new sources of antioxidants and antimicrobial agents against pan-drug resistant (PDR) pathogens of skin burn infections, methanolic extracts of nine Egyptian plants were evaluated. Total phenolic content varied from 19.48 to 65.48mg GAE/g dry weight (dw). Total flavonoid content varied from 2.90 to 11.09mg QE/g dw, while total alkaloid content varied from 18 to 60mg/g dw. Suaeda vermiculata, Varthemia candicans and Arthrocnemum glaucum showed the highest content of phenolics, flavonoids and alkaloids, respectively. The results of antioxidant (DPPH assay) activity were varied to a great extent and Varthemia candicans (90.6%) and Suaeda vermiculata (90.5%) showed the highest antioxidant activities. Antimicrobial activity was assessed against four PDR bacterial and fungal strains; namely Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans and Aspergillus flavus. Among all examined extracts, Salsola vermiculata and Suaeda vermiculata showed significant antimicrobial activity. The fatty acid composition of Salsola vermiculata and Suaeda vermiculata leaf extracts was detected using GC-MS analysis. Overall, Salsola vermiculata and Suaeda vermiculata could be used as an alternative source for the exploration of new antioxidant and antimicrobial agents that are potentially valued for food and biomedical applications.

Objective
There is an increasing incidence of Helicobacter pylori eradication therapy failure secondary to antibiotic resistance. In this study, we aimed to assess the P-glycoprotein expression levels among subjects who were H. pylori-positive and received multiple courses of eradication therapy to understand factors that may associate with their non-responses.
Methods
Eleven resistant subjects were recruited during their hospital visit for upper gastrointestinal endoscopies. H. pylori infection status was confirmed by rapid urease test and bacterial culture. P-glycoprotein expressions from the antral and duodenal biopsies were measured by Western blot. The data was compared with H. pylori-negative (n = 54) and H. pylori-positive-treatment naïve (n = 22) that were recruited earlier in another study.
Results
The resistant group showed higher relative antral P-glycoprotein expression compared to the H. pylori-negative group (p = 0.0361). Most subjects demonstrated resistance to clarithromycin (72%), metronidazole (63.6%) or both (54.5%). No significant difference was observed between the P-glycoprotein expression in H. pylori-treatment resistant and H. pylori-positive-treatment naïve groups (p = 0.319).
Conclusion
H. pylori infection induces the expression of P-glycoprotein in the antrum. This study shows a potential protective mechanism which may be exploited through the use of P-glycoprotein inducers, such as rifabutin, may be beneficial in eradication regimens.