Gastrointestinal microbiota, also known as "microflora," is a collection of microorganisms that inhabit the gastrointestinal tract. Under normal circumstances, the microbiota helps maintain intestinal homeostasis. However, some resident bacteria can transition from symbionts to pathobionts, leading to the development and progression of gastrointestinal diseases such as functional dyspepsia, severe diarrhea, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). IBS is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits, including cramping, gas, and constipation. This mini-review will briefly describe microbiota, IBS, the interrelationship between IBS and microbiota, and the therapeutic use of microbiota in treating IBS.

Objectives: Sirtuins (SIRTs) are a highly conserved family of enzymes that play an important role in cancer emergence and progression including breast cancer. In this review, changes in the expression of different SIRTs in breast cancer and their association with metastasis and cancer grade were investigated.   

Methods: This study was performed on 44 selected articles on breast cancer which were extracted from PubMed, Scopus, and Web of Science. Among the selected articles, there were 31 case-control and 13 cohort studies with a total of 7326 and 4760 participants, respectively. 

Results: In most studies SIRT1, SIRT5, and SIRT7 expression levels were higher than the controls, while the expression levels of SIRT4 and SIRT6 were lower. Elevated levels of SIRT1 was associated with increased risk of distant metastatic relapse (DMR), death, and recurrence, as well as reduced relapse-free survival (RFS). Also, there was a significant correlation between increased levels of SIRT1 and metastasis of lymph nodes and other tissues. Reduced levels of SIRT4 were associated with decreased overall survival (OS).

Conclusion: Our findings suggest that the elevated levels of SIRT1, SIRT5, and SIRT7 may have the potential value for use in the diagnosis of breast cancer. Increased levels of SIRT1 can be used as a prognostic marker.

Objectives: Diabetic nephropathy (DN) is a major complication of diabetes that requires effective treatment options. This study explores the potential benefits of saffron extract as a remedy derived from medicinal plants, focusing on its effects on key inflammatory genes—Toll-like receptor 4 (TLR-4), S100 calcium-binding protein A8 (S100A8), and High Mobility Group Box 1 (HMGB1)—as well as its role in reducing oxidative stress in the kidney tissue of rats with type 1 diabetes

Methods:  The rats were randomly divided into 8 groups of 6 each. Diabetes was induced using streptozotocin (55 mg/kg.bw). Diabetic and control groups were treated with three doses of saffron extract 100, 200 and 300 mg/kg for 60 days. Biochemical kits were used to evaluate Fasting blood Glucose (FBG), urea, creatinine, albumin, lipid profile, Malondialdehyde (MDA) and total antioxidant capacity (TAC). Expression of TLR-4, S100A8, and HMGB1 genes were evaluated by real-time PCR. ANOVA and Bonferroni post-hoc tests were used for data evaluation.

Results: Diabetes significantly impaired the FBG, lipid profile, creatinine, urea, and albumin levels (P<0.05). After treatment with the saffron extract, these parameters were significantly close to the normal range in all groups compared to the control group (P<0.05). Also, the saffron extract significantly decreased the expression levels of TLR-4, S100A8, and HMGB1 genes and improved oxidative stress markers (TAC and MDA) in kidney tissues when compared to the diabetic control group (P<0.05). In addition, the beneficial effects of saffron were dose-dependent.

Conclusion: Based on the obtained results, the saffron extract can lead to the improvement of nephropathy by reducing the expression of TLR-4, S100A8, and HMGB1 genes as well as improving oxidative stress. Thus, it may be used as an adjuvant treatment for diabetic complications.

Objectives: Acute respiratory distress syndrome (ARDS) is one of the life-threatening complications of COVID-19. The occurrence of ARDS is due to over activation of the host immune response to the virus. The purpose of this study is to investigate whether administration of intravenous immunoglobulins (IVIG) could enhance the outcomes of sever ill COVID-19 patients with ARDS.

Methods: In this randomized controlled trial in Milad Hospital of Isfahan, Iran, 88 patients randomly were assigned between May to October 2020. The patients had no significant differences in age and sex. The patients divided in two groups: the group who received IVIG and routine treatment (n=44, 50%) and the control group who just treated with routine treatment (n=44, 50%). The outcomes of patients including hospitalization duration, ICU admission period and total death occurrence besides clinical and laboratory parameters were fallowed and compared between two groups.

Results: Primary outcomes of patients including hospitalization duration (P=0.18), ICU admission period (P= 0.35), and mortality (P=0.621) had no significant difference between IVIG group and the control group. At day 3 and day 5 of IVIG administration, clinical and laboratory outcomes had been screened. The clinical parameter that improved was oxygen saturation compared to the control group (87.56 ± 6.72 vs. 86.72 ± 7.52). In cardiovascular system IVIG significantly decreased the diastolic blood pressure (P= 0.02). In terms of coagulation parameters IVIG treatment decreased PTT while it increased D-dimer but no effect on platelet count and PT have been seen. The inflammatory parameters include ESR, CRP, and IL6 had no superior changes between IVIG group and the control group. 

Conclusion: Our study demonstrated that there were no superior advantages in COVID-19 patients with ARDS who treated with IVIG.

Objectives: Alpha 1-antitrypsin (A1AT) is a single-chain glycoprotein containing 394 amino acids. It is primarily synthesized in the liver as an acute phase protein. According to recent studies, the Covid-19 virus can infect host cells by binding to the ACE2 receptor via a membrane protein. On the other hand, A1AT has the potential to inhibit neutrophil elastase and prevent the entry of the virus into host cells. Consequently, A1AT can reduce the severity and duration of Covid-19 disease.

Methods: Thirty-one hospitalized Covid-19 patients with a positive PCR test and thirty healthy volunteers with a negative test as the control group were selected. Upon hospitalization, demographic and biochemical tests were conducted for both patients and controls. Serum A1AT levels in both groups were measured using nephelometry as the reference method. Liver enzymes and total protein were also determined using commercially available kits.

Results: Serum A1AT levels in the patients were increased compared to the control group and this increase was inversely proportional to the duration of hospitalization and the relative improvement for discharge. Additionally, this elevation was correlated with qualitative C-reactive protein (CRP) levels. Serum liver enzymes, ALP, and LDH in patients were significantly higher than in the controls (P<0.05), while serum total protein in patients was significantly lower than in the controls (P<0.05).

Conclusion: These data belong to a homologous group and show a correlation between serum A1AT levels and the duration of hospitalization, as well as with qualitative CRP levels. Furthermore, the increase in A1AT is proportional to the levels of serum AST, ALT, total protein, ALP, and LDH, which may serve as an alarm for potential liver involvement in such a disease. Thus, monitoring the liver condition is warranted. 

Objectives: As a key inflammatory neuropeptide, substance p (SP), is involved in Glioblastoma multiforme (GBM) carcinogenesis and tumor progression. Thus, the proinflammatory effects of SP must be strictly regulated in GBM patients. The purpose of the study is to examine whether Hesperetin, a natural flavonoid found in citrus fruits with strong anti-inflammatory and anticancer effects, can regulate SP-induced inflammation in GBM primary human cells.

Methods: The primary human cells were derived from fresh surgically resected tissue samples of GBM patients and characterized by immunocytochemical analysis of Ki-67. MTT assay was used to evaluate cell proliferation. Apoptosis was detected by an Annexin-V/propidium iodide assay kit using flow cytometry. The levels of the specific inflammatory mediators are measured by western blotting and enzyme-linked immunosorbent assay.

Results: We observed that Hesperetin effectively reduced GBM cell viability in a dose-dependent manner which was associated with the induction of apoptosis. Obtained findings indicated SP significantly increased the protein expression of phosphorylated-NF-κB, as the main regulator of inflammatory processes, and the pro-inflammatory cytokines (IL-1β, TNF-α) while Hesperetin treatment reduced the effects of SP.

Conclusion: Taken together, our findings highlight the role of SP-induced inflammatory responses in GBM pathology and suggest that Hesperetin could be an effective therapeutic strategy in attenuating SP-associated inflammation.

Objectives: Quercetin-3-O-rhamnoside, as an effective antioxidant, exists in walnut leaves and is supposed to maintain the structural integrity of the Band 3 protein of Red blood cell (RBCs). In this context, an attempt was made to explore in-silico and in-vitro hemostatic effects of chitosan/gelatin hydrogels containing hydro-alcoholic extract of Iranian walnut leaves (Juglans regia L.), rich in quercetin-3-O-rhamnoside.

Methods: In-silico molecular docking predicted the potential interaction between quercetin-3-O-rhamnoside and band 3 protein. Hydroalcoholic extraction (1:1 water: 70%ethanol) of walnut leaves was performed in a Soxhlet extractor. The hemostatic activity from various extract concentrations (0%, 2.5%, 5%, 10%, and 20% v/v) was assayed using prothrombin time test on citrated blood samples. Gelatin/Chitosan hydrogels (3:1 and 2:1) loaded with the hemostatic concentrations were prepared by the casting method, and their adhesion ability to RBCs was tested by measuring the concentration of free hemoglobin in comparison with controls such as sterile gauze and free-hydrogel positive controls.

Results: Quercetin-3-O-rhamnoside exhibited a high affinity for Band 3 protein, presenting a binding energy of -8.39 kcal/mol compared to the standard ligand 4KU with -7.11 kcal/mol. The nine amino acids found to be important in this interaction include THR728, SER465, VAL729, ARG730, ILE531, LYS851, ILE528, PHE532, and PHE792. All hydrogels incorporating with 2.5% v/v of extract could significantly enhance RBC adhesion controls (p < 0.05).

Conclusion: The hydroalcoholic extract from Juglans regia L. may be of value as an antioxidant and hemostatic agent. Quercetin-3-O-rhamnoside is suggested to be extracted from walnut leaves, and directly incorporated into the hydrogel, and its hemostatic and antioxidant properties can be investigated at both in vitro and in vivo levels.