Study of the gut microbiome in Egyptian patients with active ulcerative colitis.

INTRODUCTION AND AIM: Ulcerative colitis (UC) is characterized by chronic, uncontrolled inflammation of the intestinal mucosa. Gut microbiota dysbiosis was reported to be a factor in intestinal inflammation. The aim of the present study was to study changes in the gut microbiome in Egyptian patients with active UC. MATERIALS AND METHODS: In this cross-sectional study, the gut bacterial microbiome of 21 UC patients and 20 control subjects was analyzed using the quantitative SYBR Green real-time PCR technique, targeting the 16S rRNA gene of selected bacterial phyla/genera and/or species. RESULTS: UC patients showed marked dysbiosis evidenced by a significant decrease in the Firmicutes and F. prausnitzii anti-inflammatory bacteria. The Firmicutes/Bacteroidetes ratio was also lower in the UC cases (1.65), compared with the healthy controls (2.93). In addition, the UC cases showed a statistically significant decrease in Ruminococcus, compared with the control group. However, there were no statistically significant differences between UC patients and the controls, regarding A. muciniphila, Bifidobacterium, Lactobacillus, Bacteroides, and Prevotella. One UC case was positive for the pathogenic bacterium, Clostridioides difficile, with low relative abundance. CONCLUSION: The current study showed differences in the gut microbiome of UC patients, compared with healthy controls. This may help in identifying the gut microbiome and specific bacterial changes that can be targeted for treatment of UC.

Triple-action of the standardized antidiabetic polyherbal extract; Synacinn™ through upregulation of GLUT4 and inhibition of DPP(IV), α-amylase, and α-glucosidase activity.

INTRODUCTION: Synacinn™ is a standardized polyherbal supplement for diabetes mellitus which is formulated from Andrographis paniculata, Curcuma xanthorrhiza, Cinnamomum zeylanicum, Eugenia polyantha, and Orthosiphon stamineous. MATERIALS AND METHODS: This study aimed to elucidate the antidiabetic potential of Synacinn™ on three specific actions, including 1) the insulin sensitivity and glucose transport on dexamethasone-induced insulin-resistance 3T3-L1 adipocytes, 2) the inhibitory capacity on postprandial enzyme activity (α-amylase and α-glucosidase), and 3) the inhibitory activity of hepatic DPP(IV) enzyme. RESULTS: Results showed that insulin resistance of 3T3-L1 adipocytes may be developed by prolonging the exposure of 1µg/ml of dexamethasone for >48 hours. The insulinresistance condition was minimized by the treatment of 10 µg/ml of Synacinn™ which significantly improved the insulin-stimulated glucose utilization by 10.6%. Meanwhile, insulin-stimulated glucose utilization in normal adipocytes was also attenuated by 9.2%. At the cellular level, Synacinn™ attenuated glucose utilization mainly by upregulating GLUT4 protein expression by 1.71 fold. Additionally, Synacinn™ is a potent inhibitor for the activity of α-amylase and α-glucosidase with IC50 of 0.467 mg/mL and 0.245 mg/mL, respectively. Synacinn™ also controlled the glycemic index through inhibition of hepatic DPP(IV) enzyme with IC50 of 1.11 mg/mL. CONCLUSION: Results suggested that Synacinn™ reduced diabetes mellitus through sensitizing the cellular glucose utilization, reducing the postprandial carbohydrate degradation, and inhibiting the hepatic DPP(IV) enzyme function.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes.

Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes

@#Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Severe asymptomatic hypophosphataemia in a child with T-acute lymphoblastic leukaemia.

Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients. Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could lead to impairment in multiple organ systems, which include the respiratory, cardiovascular, neurological and muscular systems and haematological and metabolic functions. Hypophosphataemia is defined as plasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroups of mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65 mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemia include inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphate loss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated with haematological malignancies has been reported infrequently. We report here a case of asymptomatic severe hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia. A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL). His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenase levels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeated analysis. The child had no symptoms related to low phosphate levels. The possible causes of low phosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started and the serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed to shift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidly proliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous and lymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case of severe asymptomatic hypophosphataemia in a child with ALL.

Glutathione S-transferase Mu-1 gene polymorphism in Egyptian patients with idiopathic male infertility.

The aim of this study was to examine whether an association exists between glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and idiopathic male infertility. Sixty men with primary idiopathic infertility and 60 fertile men, serving as controls, were recruited for the study. The polymorphism was analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of GSTM1 null genotype was observed to be higher in infertile men 40% in comparison with 33.3% in the fertile men, but this difference was not statistically significant. There was statistically significant difference between cases and controls as regards GSTM1 genotype distribution ((MC) P = 0.006*) in GSTM1-positive men. Patients with the GSTM1 null genotype had significantly lower sperm concentrations and total sperm count when compared with patients with GSTM1-positive genotype. In the control group, men with GSTM1 null genotype had significantly lower sperm concentrations but not total sperm count when compared with men with GSTM1-positive genotype. The results of this study suggest a possible negative effect of GSTM1 null genotype on the spermatogenic potential of the testis.

Clinical, laboratory and genetic assessment of patients with congenital bilateral absent vas deferens.

The aim of this study was to assess the prevalence of Δ-F508 mutation and 5T allele in a sample of Egyptian patients having congenital bilateral absent vas deferens (CBAVD), to correlate between genotype and phenotypic genital pattern, and to demonstrate the value of micro-assisted reproduction in them. The study included thirty patients with CBAVD and 30 fertile controls. Clinical, laboratory and radiological examinations of the patients were performed. Genetic assessment of patients and controls as regards Δ-F508 mutation and 5T allele was done. Trials of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) were carried out for the patients. Δ-F508 mutation was present in 40% and 5T allele was detected in 46.6% of the patients. On the other hand, all the control group was negative as regards Δ-F508 mutation, while 5T allele was detected in 10% of them. The total fertilisation rate was 75% and pregnancy rate was 60% with no significant difference in fertilisation and pregnancy rates between cases positive for Δ-F508 or 5T allele and others. It is evident that Δ-F508 mutation and 5T allele play important roles in the pathogenesis of CBAVD in Egyptians. TESE/ICSI is a beneficial method to enable these patients to father children of their own.