Human Gut Microbiome Before and After Bariatric Surgery in Obese Patients with and Without Type 2 Diabetes.

BACKGROUND: Bariatric surgery, a significant intervention for obesity, may influence weight loss through changes in gut microbiota, particularly the Firmicutes and Bacteroidetes. This study explores these potential shifts and their metabolic implications. MATERIALS: We conducted a cross-sectional study involving patients who had undergone bariatric surgery. Stool samples were collected at baseline, 3 months, and 6 months post-operation. We performed DNA extraction and quantified the bacterial phyla Firmicutes and Bacteroidetes to assess changes in the gut microbiota over time. RESULTS: Our research revealed a significant alteration in the gut microbiota following bariatric surgery. In diabetic individuals, there was a marked increase in the average number of Firmicutes bacteria at both 3 and 6 months post-operation, compared to pre-surgery levels. In contrast, non-diabetic subjects experienced a notable decrease in Firmicutes during the same timeframe. Regarding Bacteroidetes bacteria, the trend was reversed; diabetic patients showed a significant reduction, while non-diabetics exhibited an increase after the surgery. These findings highlight the dynamic changes in gut microbiota composition associated with bariatric surgery and its potential link to metabolic changes post-operation. CONCLUSION: These findings suggest that obesity alters the gut's microbial composition. The observed bacterial fluctuations, particularly in the dominant Firmicutes and Bacteroidetes groups, are likely contributors to the weight loss experienced post-surgery. This alteration in gut bacteria underscores the complex interplay between microbiota and metabolic health, highlighting potential avenues for therapeutic intervention.

Ovarian Endocrine Status and ART 0utcomes in Women within PCOS Based on Different Testosterone Levels.

Background: It is estimated that in women at reproductive age, the risk of polycystic ovary syndrome (PCOS) is about 5-21%. In PCOS cases with ovulation dysfunction, assisted reproductive techniques (ART) are useful for infertility treatment. Objective: This study aimed to evaluate the ART outcome in infertile PCOS women based on different testosterone levels. Finally, the relationships between testosterone in different levels and reproductive parameters including endocrine status, the response of ovaries, and pregnancy outcomes were assessed. Methods: In this retrospective study, 352 infertile PCOS women were examined. The women were categorised into five groups according to their testosterone levels: A = T < 0.4, B = 0.4 < T > 0.6, C = 0.6 < T > 0.8, D = 0.8 < T > 1.0 and E = T > 1.0 ng/dL. All study cases were in similar hyper-stimulation protocol and finally, hormonal profile and ART outcomes were compared between testosterone levels. P value ≤ 0.05 was statistically significant. Results: In testosterone levels >1.0, the levels of anti-mullerian hormone (AMH) and luteinising hormone (LH) were higher than in other testosterone level groups. AMH (P = 0.05) and LH (P = 0.001) levels showed significant differences. No correlation was present between testosterone levels and ART outcomes, including stimulation duration, endometrial thickness, oocyte numbers, numbers of matured oocytes, number of obtained embryos, fertilisation rate, implantation rate clinical pregnancy and abortion rate. Conclusions: Serum testosterone levels did not show any correlation with pregnancy outcomes in ART cycles of PCOS. However, basal testosterone levels are a good predictor for ovarian reserve and ovarian response. Consequently, we suggest that some prospective studies must be designed to approve the role of testosterone in the prediction of the outcome of pregnancy in ART cycles.

Anti-aging effects of the pistachio extract on mesenchymal stem cells proliferation and telomerase activity.

PURPOSE: Using mesenchymal stem cells (MSCs) is a promising method in regenerative medicine. Limited proliferation and aging process of MSC are the most common problems in MSCs application. In the present study, we intend to investigate the anti-aging properties of pistachio pericarp in bone marrow-derived MSCs of old male rats. MATERIALS AND METHODS: First, 1000, 2000, and 3000 µg/mL AEPP were used to treat MSCs derived from bone marrow for 24 h at 37 °C. Then, cell viability, population doubling time, the percentage of senescent cells, telomere length, telomerase activity, and the expression of TRF1 and RAP1 when bone marrow-derived MSCs treated with AEPP were investigated. RESULTS: The results showed that cell viability increased when MSCs derived from bone marrow were treated with 2000 and 3000 µg/mL AEPP, indicating this extract may stimulate proliferation. The population doubling time was also enhanced with an increase in AEPP concentration. Importantly, an increase in AEPP concentration significantly reduced senescent cell percentage. Telomere length, telomerase activity, and the expression of anti-aging genes were significantly increased with the increase of AEPP dose. CONCLUSION: Taken together, AEPP has been used as a natural compound with excellent proliferation and anti-aging ability in MSCs. As new therapeutic candidates with promising effects, it can be used with high safety by multiplying cells and delaying the aging process. However, more studies are needed and the anti-aging effects of this extract should be well confirmed in animal models and clinical trials.

Nanoliposomal formulation of pistachio hull extract: preparation, characterization and anti-cancer evaluation through Bax/Bcl2 modulation.

BACKGROUND: Pistachio is one of the main crops in Iran. Pistachio green hull, as a by-product of this fruit, is obtained in large quantities after the processing of pistachios. This novel work was designed to examine the possible anti-cancer impact of the pistachio hull extract in the liposomal form (PHEL) on HepG2 cells. METHODS AND RESULTS: The thin-film hydration approach was used for preparing liposomes and the physicochemical features of the liposomes were subsequently characterized. Afterward, apoptosis and the expression of genes related to apoptosis were assessed using flow cytometry assay and quantitative real-time polymerase chain reaction (qPCR), respectively. According to the results, the size range of PHEL was between 198 and 201 nm with a negative surface charge of - 39.2 to - 42.9 mV. As revealed by the flow cytometry results, this liposomal extract exhibits good potential for the induction of apoptosis. Moreover, the qPCR results demonstrated the up-regulation of p53 and Bax expressions and the down-regulation of Bcl-2 expression with an associated Bax/Bcl-2 ratio up-regulation. CONCLUSION: The flow cytometry and real-time PCR results indicated the potential of this liposomal extract as an anti-cancer drug candidate for the treatment of liver cancer in the future, and the mitochondrial pathway involving the up-regulation of the Bax/Bcl-2 ratio can mediate its impact.

The immune response against Toxoplasma gondii in BALB/c mice induced by mannose-modified nanoliposome of excreted/secreted antigens.

This study aimed to compare the immune response against Toxoplasma gondii (T. gondii) in BALB/c mice induced by excreted/secreted (E/S) antigens and mannose-modified nanoliposome of E/S antigens. Here, E/S antigens and mannose-modified nanoliposome of E/S antigens were firstly prepared, and then BALB/c female inbred mice were separately immunized. In the next step, anti-E/S antigen antibodies and the relative expression levels of IL-10 and IL-12 mRNA were detected by ELISA and real-time PCR, respectively. After immunization, mice were intraperitoneally challenged with 102 tachyzoites of T. gondii, and the survival rate was recorded. The ELISA analysis showed significant differences between the levels of anti-E/S antigen antibodies in the mice immunized by E/S antigens and those immunized by mannose-modified nanoliposome of E/S antigens at days 7, 10, 20, 25, and 30 (P < 0.05). Real-time PCR analysis showed that the relative expression of IL-10 was significantly decreased during 20 days. Yet, the relative expression of IL-12 was significantly increased during 20 days (P < 0.05). In T. gondii challenge test, significant differences were found between the survival rates of mice immunized by E/S antigens and mice immunized by mannose-modified nanoliposome with E/S antigens. This project evidenced that mannose-modified nanoliposome of E/S antigens induced a more powerful immune response against T. gondii in BALB/c mice when compared with excreted/secreted antigens alone.

The Effects of Hydro-Alcoholic Extract of Fenugreek Seeds on the Lipid Profile and Oxidative Stress in Fructose-Fed Rats.

BACKGROUND: Metabolic syndrome (MetS) is a complex clinical disorder that can lead to an increase in oxidative stress. Patients with this syndrome are at risk of diabetes and cardiovascular disease. The Trigonella foenum-graecum L. (fenugreek) plant has many therapeutic effects, including anti-diabetic and antioxidant. The present study aimed to investigate the effects of the hydro-alcoholic extract of fenugreek seeds (HEFS) on dyslipidemia and oxidative stress due to high-fructose diet-induced MetS. METHODS: In this experimental study, to induce MetS, animals received water containing 20% fructose for 8 weeks. After induction of MetS, 48 male Wistar rats (200-250 g) were randomized into six groups. HEFS was administered to animals at doses of 100 and 200 mg/kg orally for 4 weeks. Animal blood samples were collected to measure biochemical and antioxidant parameters of fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC). RESULTS: The findings showed that the serum levels of FPG, TC, LDL-C, TG, and MDA were significantly reduced in HEFS-exposed groups compared with the control group (P<0.05). Also, significant increases in HDL-C, GPX, CAT, and TAC levels (P<0.05) were observed. CONCLUSION: Our results revealed that treatment with HEFS increases the levels of antioxidant enzymes, decreases FPG level, and at the same time, modifies the lipid profile in MetS. Therefore, HEFS may help to alleviate the risk of some chronic complications of this disease.

Resistance pattern of Escherichia coli to levofloxacin in Iran: a narrative review.

Fluoroquinolones (FQs) are widely used in the treatment of infections caused by Escherichia coli. FQs are broad spectrum antibiotics with high tissue penetration, and ease of use. Therefore, given the concerns existing about drug resistance, we aim to review the latest findings about resistance patterns to levofloxacin (LVX) along with other FQs in E. coli infections in different parts of Iran. Evidence shows that quinolones have been used in Iran for nearly 50 years, and that 0-65% of E. coli isolates show resistance to FQs. In the western parts of Iran, the highest rate of resistance to LVX (66.7%) has been reported among patients having urinary tract infections with E. coli isolates. Few studies and information exist on the antimicrobial resistance of E. coli to LVX in different geographical locations of Iran. However, the findings of various studies on this subject show that E. coli resistance to LVX is more in the western part of Iran than in central and southern regions, but it is similar among inpatients and outpatients. Therefore, it is reasonable advisable to limit the overuse, inappropriate prescription, and self-medication of LVX to prevent the induction of FQ-resistant strains. Accordingly, in order to obtain a clearer image of resistance to FQs, especially LVX in E. coli in Iran, more extensive investigations in different geographical locations and periods of time are required. In addition, antimicrobial stewardship would be helpful in this regard.

Effective Treatments for Bladder Cancer Affecting CXCL9/CXCL10/CXCL11/CXCR3 Axis: A Review.

Bladder cancer (BC) originates mainly from the epithelial compartment of the bladder, which is defined as transitional cell carcinoma or urothelial cell carcinoma. About 70% of patients with BC will survive five years from diagnosis. Previous studies revealed that the immune system and its mediators, particularly chemokines, play a crucial role in modulating responses against BC. Chemokines, which serve as chemoattractants for leukocytes, are small proteins that can initiate inflammatory and anti-inflammatory immune responses and also are associated with many aspects of both regulation and progression of mentioned responses. Additionally, these immune mediators can interfere with the other tumor-related processes, including tumor proliferation, neovascularization, and metastases. Among these chemokines, CXC chemokines, including CXCL9, CXCL10, and CXCL11, are recognized as the main ligands of C-X-C motif chemokine receptor 3 (CXCR3) and contribute to related immune responses after therapeutic strategies for BC. Evidence suggests that the production of these chemokines can have two important implications. First, these mediators can trigger the accumulation of CD8+ T cells that can contribute to the elimination of the tumor. Secondly, the production of these chemokines by tumor tissue may trigger the migration and activation of immune cells including myeloid-derived suppressor cells and regulatory T cells, which act in favor of the tumor and its progress. Therefore, in this review, we describe the latest therapeutic approaches based on targeting this axis's components and subsequent immune phenomenon.

Physicochemical properties and health benefits of pistachio nuts.

The genus of Pistacia plant systematically fits into the family of Anacardiaceae. Pistachios contain protein, carbohydrate, dietary fibers, fat, folic acid, vitamin K, magnesium and potassium, gama-tocopherols, phytochemicals, and polyphenols. Collectively, these constituents have been shown to possess antioxidant and anti-inflammatory functions to improve overall health when consumed as a healthy diet. We searched the following keywords within the literature databases: pistachio, heart disorders, lipids, weight, antioxidants, and allergy. Further searching theses keywords, we have found 50 articles in PubMed, 40 articles in ISI web of knowledge and 30 articles in Google Scholar. We have selected 100 articles, among them 80 articles were used as the references of this review. In the current article, we have discussed the most recent data published regarding the regulatory effects of pistachios on several clinical states such as heart related disorders, hyperlipidemia, hypertension, vascular stiffness and endothelial and gut functions, weight management, glucose metabolism, kidney function and finally allergies.

Indole itself and its novel derivative affect PML cells proliferation via controlling the expression of cell cycle genes.

Recently the role of indole and pyran rings in carcinogenesis has been well studied. Here we studied the effects and the possible mechanisms of the action of basal indole (I3A) and its novel indole derivative (C19H15F3N2O) on inhibition of proliferation cells in acute promyelocytic leukemia NB4 cell line by examining the expression of cell cycle genes. We treated NB4 cells with concentration of C19H15F3N2O for 24-72 h. The MTT and PI/Annexin V examinations were employed for assessment of the proliferation and apoptosis of NB4 cells. Both of Cyclin D and P21 were detected by the Real-time PCR. The western blotting analysis was also performed to show the protein levels for P21. A difference was regarded significant if p-value was less than 0.05. MTT assay showed that 15.12-1000 µg/mL C19H15F3N2O caused a time and concentration-dependent inhibition of NB4 cell proliferation. Exposure to higher concentrations of C19H15F3N2O resulted in significantly increased apoptosis rate in NB4 cells. RT PCR showed that C19H15F3N2O has up-regulated the expression of P21 and down-regulated the expression of Cyclin D. Western blotting experiments also demonstrated that the P21 expression in C19H15F3N2O treated cells has significantly increased, where compared with either untreated control cells or I3A treated cells. This newly (C19H15F3N2O) was able to inhibit NB4 cells proliferation and causes apoptosis of these cells more than I3A, and these effects are probably facilitated via cell cycle arrest. C19H15F3N2O might probably be introduced as a promising organic therapeutic reagent against APL.

Nano-scale drug delivery systems for antiarrhythmic agents.

Arrhythmia means the heart is beating too fast, too slow, or with an irregular pattern. Due to the side effects and low bioavailability of many antiarrhythmic drugs, nano-encapsulation has been widely used for their targeted delivery. Lipid nanocapsules, nano liposomes, nano niosomes, solid lipid nanoparticles and polymeric nanoparticles are common nano-carriers used for this purpose. The aim of this article is to summarize some of nano systems used for the specific delivery of antiarrhythmic agents to target tissues. At first, nanotechnology and its applications in drug delivery are described in brief. Then, some information on arrhythmias and antiarrhythmic drugs are provided. Finally, the nano drug delivery systems are explained and examples of their applications in encapsulation of antiarrhythmic drugs are presented.

The cytotoxicity effects of a novel Cu complex on MCF-7 human breast cancerous cells.

A variety of biological activities, such as anti-microbial and anti-tumor properties was reported for 1,10-phenanthroline and its copper complexes. In this study, the anti-proliferative activity of a novel  [Cu(L)(phen)] complex was investigated on MCF-7 breast cancer cells using MTT assay. Since chemotherapy is lake of ability to distinguish between normal cells from cancerous cells, therefore we also investigated the effect of  [Cu(L)(phen)] complex on normal L929 cells. The results showed that following 24 and 48 h exposure of cells with  [Cu(L)(phen)] complex, the IC50 values for MCF-7 were significantly lower than that recorded for L929 and normal cells were less sensitive than cancerous cells to the complex. Additionally, the  [Cu(L)(phen)] complex displayed a time- and concentration-dependent cytotoxic response, with MCF-7 and L929 cells. Also flow cytometry findings suggest that  [Cu(L)(phen)] complex is capable of decreasing cancer cell viability through apoptosis and did not efficiently activate the necrosis process.

WITHDRAWN: The anti-cancer properties in parallel with toxic effects of indole-3-carbinol derivatives.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Circulatory Levels of C-X-C Motif Chemokine Ligands 1, 9, and 10 Are Elevated in Patients with Ischemic Stroke.

OBJECTIVE: Inflammation plays a significant role in the development of ischemic stroke. CXC chemokines play pleiotropic roles in prolonged leukocyte locomotion, astrocyte migration/activation, and neural attachment/sprouting in response to focal stroke. In this study, we aimed to explore the changes in serum levels of three chemokines, C-X-C motif chemokine ligand 1 (CXCL1), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), in ischemic stroke patients at the time of admission and before discharge from the hospital ward. MATERIALS AND METHODS: In this study, we recruited 43 unrelated ischemic stroke patients using an easy convenience method or accidental sampling which is a type of non-probability sampling that involves the sample being drawn from that part of the population that is close to hand. We also enrolled 50 genetically unrelated healthy controls showing no history of neurologic, cardiovascular, or inflammatory diseases. Serum levels of the considered chemokines were measured by enzyme-linked immunosorbent assay (ELISA) in patients and healthy controls. RESULTS: No significant difference was observed in ischemic stroke patients following hospitalization and prior discharging from the hospital; however, there was a significant difference in serum levels of CXCL9 and CXCL10 between patients and healthy controls. We also found that the level of the chemokine was not related to gender or medical therapy. It appears that CXCL9 and CXCL10 are more predisposing factors and play a direct role in stroke considering that they were higher in patients than in healthy controls. CONCLUSION: We believe that this study might be used as a basis for further studies on more effective medication regimens to prevent the onset and subsequent complications of stroke. However, these mediators are useful diagnostic and prognostic tools rather than therapeutic tools.

The novel Indole-3-formaldehyde (2-AITFEI-3-F) is involved in processes of apoptosis induction?

AIM AND OBJECTIVES: Balancing between Bax and Bcl-2 plays critical roles in both proliferation and self-renewal activation of cancer cells. Indole-3-formaldehyde derivatives limit the growth and facilitate cell death in different cell systems. In this study, we introduced a novel indole derivative (2-AITFEI-3-F) with tendency to facilitate apoptosis in NB4 line in comparison to basal Indole-3-formaldehyde (I3F). METHODS: The NB4 cells were cultured in RPMI1640 medium contained 2-AITFEI-3-F and I3F (15.12-1000µg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was assessed by trypan blue staining technique and MTT assay. The fold changes of Bax/Bcl-2 expression against ß-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of Bax and Bcl2 at protein level. Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P<0.01). RESULTS: There was a significant difference in cell viability, when various concentrations of 2-AITFEI-3-F (but similar to I3F) were used for 24, 48 and 72h in comparison to I3F regarding the cellular viability (P<0.05). Real time PCR and Western blotting analysis indicated that the gene and protein expression level of Bcl-2 down-regulated while Bax was up-regulated in compare to untreated control cells and cells treated with I3F (P<0.01). CONCLUSION: According to these findings, the novel indole derivative 2-AITFEI-3-F probably triggered apoptosis of NB4 cells by modulating Bax/Bcl-2 ratio. Furthermore, the 2-AITFEI-3-F had markedly displayed anti-cancer activity than I3F.

Persian shallot, Allium hirtifolium Boiss, induced apoptosis in human hepatocellular carcinoma cells.

This study investigated the potential of Persian shallot extract as an anticancer agent in HepG2 tumor cell line, an in vitro human hepatoma cancer model system. The inhibitory effect of Persian shallot on the growth of HepG2 cells was measured by MTT assay. To explore the underlying mechanism of cell growth inhibition of Persian shallot, the activity of Persian shallot in inducing apoptosis was investigated through the detection of annexin V signal by flow cytometry and expression of some apoptosis related genes such p21, p53, puma, caspase-8 family-Bcl-2 proteins like bid, bim, bcl-2 and bax were measured by real-time PCR in HepG2 cells. Persian shallot extract inhibited the growth of HepG2 cells in a dose-dependent manner. The IC50 value (inhibiting cell growth by 50%) was 149 µg/ml. The results of real-time PCR revealed a significant up-regulation of bid, bim, caspase-8, puma, p53, p21 and bax genes and a significant downregulation of bcl-2 gene in HepG2 cells treated with Persian shallot extract significantly. Therefore, this is the first report on an increased expression of bid, bim, caspase-8, puma, p53, p21 and bax genes and down regulation of bcl-2 gene indicating that the Persian shallot extract possibly induced the process of cell death through the intrinsic and extrinsic apoptosis pathways and triggers the programmed cell death in HepG2 tumor cell lines by modulating the expression of pro-/anti-apoptotic genes. Furthermore, we showed that Persian shallot extract increased annexin V signal and expression, resulting in apoptotic cell death of HepG2 cells after 24 h treatment. Therefore, according to the results of this study, the Persian shallot extract could be considered as a potential candidate for production of drug for the prevention or treatment of human hepatoma.

High-level extracellular secretion of organophosphorous hydrolase of Flavobacterium sp. in Escherichia coli BL21(DE3)pLysS.

Organophosphorus (OPs) compounds are widely used in many pesticides, insecticides, and chemical nerve agents. These compounds are hazardous for humans and the environment. There are many reports on detoxification of these compounds, among them enzymatic cleavage of these compounds with organophosphorus hydrolase (OPH) has been taken into more consideration. Several studies have been performed to improve OPH secretion in Escherichia coli by different signal peptides, but have not been successful. In this study, to achieve the extracellular secretion of OPH in E. coli, the complete opd gene along with its native signal peptide was codon optimized and expressed in E. coli BL21(DE3)pLysS. The culture medium showed OPH activity after 2, 4, and 6 H of induction time. The extracellular secretion of OPH was also confirmed by SDS-PAGE and Western blot analysis. The effects of different factors in growth medium were also investigated regarding expression and extracellular secretion of OPH. It appears that the secretion of OPH into the extracellular medium is highly affected by culture conditions. Therefore, our results revealed that the recombinant OPH was successfully secreted into the extracellular medium. This secretion system can be considered as a high efficiency biocatalyst for detoxification of OPs compounds.