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Mycobacterium tuberculosis (M.tb), the causative agent of Tuberculosis, is an intracellular bacterium well known for its ability to subvert host energy and metabolic pathways to maintain its intracellular survival. For this purpose, the bacteria utilize various mechanisms of which extracellular vehicles (EVs) related mechanisms attracted more attention. EVs are nanosized particles that are released by almost all cell types containing active biomolecules from the cell of origin and can target bioactive pathways in the recipient cells upon uptake. It is hypothesized that M.tb dictates the processes of host EV biogenesis pathways, selectively incorporating its molecules into the host EV to direct immune responses in its favor. During infection with Mtb, both mycobacteria and host cells release EVs. The composition of these EVs varies over time, influenced by the physiological and nutritional state of the host environment. Additionally, different EV populations contribute differently to the pathogenesis of disease at various stages of illness participating in a complex interplay between host cells and pathogens. These interactions ultimately influence immune responses and disease outcomes. However, the precise mechanisms and roles of EVs in pathogenicity and disease outcomes remain to be fully elucidated. In this review, we explored the properties and function of EVs in the context of M.tb infection within the host microenvironment and discussed their capacity as a novel therapeutic strategy to combat tuberculosis.

The signs and symptoms of chronic urticaria (CU) are caused by the activation and degranulation of skin mast cells (MCs). Recent studies have added to our understanding of how and why skin MCs are involved and different in CU. Also, novel and relevant mechanisms of MC activation in CU have been identified and characterized. Finally, the use of MC-targeted and MC mediator-specific treatments has helped to better define the role of the skin environment, the contribution of specific MC mediators, and the relevance of MC crosstalk with other cells in the pathogenesis of CU. Here, we review these recent findings and their impact on our understanding of CU, with a focus on chronic spontaneous urticaria (CSU). Also, we highlight open questions, issues of controversy, and unmet needs, and we suggest what studies should be performed moving forward.

Abstract Background N-acetylcysteine (NAC) is a tolerable and safe drug capable of reducing free radicals and other oxidants. We included 74 individuals with ischemic stroke in this randomized, single-blind clinical trial and placed them into intervention (n = 37) and control (n = 37) groups. In the intervention group, in addition to standard treatment for ischemic stroke, they received NAC at a dose of 100 mg/kg bolus and then at a dose of 10 mg/kg/h for 10 h. The control group received only standard stroke treatment. Blood samples were taken before starting NAC and standard stroke treatment and 24 h after receiving the drug to measure the catalase, paraoxonase, malondialdehyde (MDA), neopterin, total antioxidant capacity (TAC), and total oxidant status (TOS) parameters. The National Institutes of Health Stroke Scale (NIHSS) was also calculated before and after 24 h, 2 weeks, 1 month, and 3 months after starting the drug. Results There was no significant difference between the results of parameters before and after standard treatment in control group; however, NAC could significantly reduce TOS (P = 0.02) in the intervention group. Moreover, NAC administration could notably decrease NIHSS calculated at each time point when compared to control group. After subgrouping the intervention group, NAC could increase catalase (P

Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways.

We investigated the probiotic potential of a microencapsulated Enterococcus faecium ABRIINW.N7 for control of Streptococcus agalactiae infection in hybrid (Oreochromis niloticus × Oreochromis mossambicus) red tilapia. A two-phase experiment approach was completed in which E. faecium bacteria were propagated, from which a culture was isolated, identified using molecular techniques, and microencapsulated to produce a stable commercial fructooligosaccharide (FOS) and fenugreek (Fk) product of optimal concentration. The FOS and Fk products were assessed in a 90-days in vivo challenge study, in which red hybrid tilapia were allocated to one of five treatments: (1) No Streptococcus agalactiae (Sa) challenge (CON); (2) Sa challenge only (CON+); (3) Sa challenge in a free cell (Free Cell); (4) Sa challenge with 0.8% (w/v) Alginate; (5) Microencapsulated FOS and Fk. In vitro results showed high encapsulation efficiency (≥98.6 ± 0.7%) and acceptable viability of probiotic bacteria within the simulated fish digestive system and high stability of viable cells in all gel formulations (34 < SR%

Chronic urticaria (CU) is a mast cell-driven chronic inflammatory disease with a female predominance. Since CU affects mostly females in reproductive age, pregnancy is an important aspect to consider in the context of this disease. Sex hormones affect mast cell (MC) biology, and the hormonal changes that come with pregnancy can modulate the course of chronic inflammatory conditions, and they often do. Also, pregnancy-associated changes in the immune system, including local adaptation of innate and adaptive immune responses and skewing of adaptive immunity toward a Th2/Treg profile have been linked to changes in the course of inflammatory diseases. As of now, little is known about the effects of pregnancy on CU and the outcomes of pregnancy in CU patients. Also, there are no real-life studies to show the safety of urticaria medications during pregnancy. The recent PREG-CU study provided the first insights on this and showed that CU improves during pregnancy in half of the patients, whereas it worsens in one-third; and two of five CU patients experience flare-ups of their CU during pregnancy. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends adopting the same management strategy in pregnant and lactating CU patients; starting treatment with standard doses of second-generation (non-sedative) H1 antihistamines, to increase the dose up to 4-folds in case of no response, and to add omalizumab in antihistamine-refractory patients; but also emphasizes the lack of evidence-based information on the safety and efficacy of urticaria treatments during pregnancy. The PREG-CU study assessed treatments and their outcomes during pregnancy. Here, we review the reported effects of sex hormones and pregnancy-specific immunological changes on urticaria, we discuss the impact of pregnancy on urticaria, and we provide information and guidance on the management of urticaria during pregnancy and lactation.

Background: In addition to cellular and molecular mechanisms involved in the pathogenesis of asthma, mounting evidences demonstrate that single nucleotide polymorphisms (SNPs) in asthma relevant genes have a role in conferring susceptibility to the disease. CHI3L1 is secreted from macrophages, neutrophils, and airway epithelial cells through an IL-13 related mechanism and contributes to tissue remodeling during asthma. Aim of study was to investigate the possible association of rs4950928 SNP in Chiti3L1 gene with predisposition to allergic asthma in Iranian Northwestern Azeri population. Materials and methods: Frequency of genotypes and alleles of rs4950928 SNP in Chiti3L1 gene was determined using TaqMan genotyping method in 190 patients with asthma and 190 healthy controls. Results: Genotype analyzing showed that CC genotype is more frequent (68.4%) among case group vs 57.9% in control group while GG genotype is more abundant (7.9%) among control group vs 3.2% in case group. Furthermore, according to odds ratio (case/ control = 0.611), C allele could be the risk allele whereas G allele can be considered as the protective allele. Conclusion: There is a significant relationship between CHI3L1 rs4950928 (-131 C/G) polymorphism and asthma in studied population (P=0.038,

Orosomucoid 1-like 3 (ORMDL3) gene, located on chromosome 17q21, is an asthma candidate gene that encodes ORMDL3. This molecule has been reported to play a role in airway remodeling and bronchial hyper-responsiveness. In this study, we aimed to investigate the possible association of ORMDL3 single nucleotide polymorphism (SNP) (rs12603332) with susceptibility to allergic asthma in Iranian Northwestern Azeri population. 193 asthmatic patients and 185 normal individuals were included. Genomic DNA was extracted and genotyping was performed by standard restriction fragment length polymorphism-polymerase chain reaction RFLP-PCR method using BstUI restriction enzyme. Our results showed dominant presence of TC genotype and C allele in both patients (49.2% and 59.8%, respectively) and controls (48.6% and 60%, respectively). Frequency of genotypes and alleles showed no significant difference between two groups (p=0.994 and p=1.00, respectively). None of alleles could be defined as risk allele for allergic asthma (OR=0.99, 0.88-1.12, 95% CI). We failed to show significant association between ORMDL3 rs12603332 with predisposition to allergic asthma in Iranian Northwestern Azeri population. More studies with larger number of participants should be done to find more reliable results for such association.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic enzymes that play a role in extracellular matrix (mainly collagen) degradation and remodeling. MMPs are not only causes of the increase rewarding effects of drugs, but also act as pro-addictive agents. In this research, 22 morphine and 20 methamphetamine-dependent patients included and their serum levels and activity of MMP2 and 9 were assessed by ELISA and gelatin zymography and compared with those of 23 healthy individuals as a control group. Our findings showed a significant increase in serum levels and activity of MMP-2 in opium and methamphetamine groups in comparison with the control group. Moreover, unlike MMP-2, serum levels and activity of MMP-9 in both case groups found to be decreased. This study showed that long-term abuse of opium and methamphetamine changes the activity and serum levels of MMP9 and MMP2. The effects of methamphetamines and opium are associated with an increase in extracellular dopamine levels in the brain, achieved by facilitating the release of dopamine from pre-synaptic nerves. Our findings showed that serum levels and activities of MMP-9 and MMP-2 could be considered as alternative valuable biomarkers from those investigated of pro-addictive or anti-addictive factors in dependent patients.

Objective: Fc receptor - like (FCRL) 3 is a transmembrane molecule that has putative roles in B-cell biology, and could be involved in antibody-mediated immune disorders including allergy and asthma, and also in B-cell malignancies. We aimed to investigate the possible association of rs7528684 SNP (-169C/T or FCRL3_3) in FCRL3 gen with predisposition to allergic asthma in Azeri population of Iran. Material and Methods: Frequency of genotypes and alleles of rs7528684 SNP in FCRL3 gene was determined using TaqMan genotyping method in 191 asthmatic patients and 186 healthy controls. Results: The most frequent genotype in patients and control groups were CT (n=81, 42.4%) and TT (n=76, 40.9%) respectively. Statistical analysis showed no significant difference in genotype frequency (p=0.81) and also in frequency of C and T alleles (p=0.52) between two groups. Conclusion: Our results revealed no association between rs7528684 SNP with susceptibility to allergic asthma in Azeri population of Iran. [ABSTRACT FROM AUTHOR]

Abstract Objective In present study, the effects of the leaf extract of Pyrus biossieriana Buhse on tert-Butyl hydroperoxide (t-BHP) induced toxicity in the HepG2 cell line were investigated. Results HepG2 cells were exposed to different concentrations of both extract (1.5, 2.0, and 2.5 mg/mL) and t-BHP (100, 150, and 200 μM). The total flavonoid and phenolic contents, the cell viability, lipid peroxidation, NO generation, and the total antioxidant capacity in cell media were assessed. The amount of arbutin was estimated 12.6% of the dry weight of leaves (equivalent to 126 mg/g). Additionally, the amounts of flavonoids and phenols in extract were estimated 119 mg/g and 418 mg/g, respectively. The cells incubated with t-BHP showed a significant decrease in survival (p

Prostate cancer (PCa) pathology has been linked to vitamin D, vitamin D receptors (VDRs), and vitamin D binding proteins (VDBPs). We sought to investigate the association between VDR rs2228570 and rs1544410 as well as VDBP rs7041 polymorphisms and serum 25-hydroxyvitamin D (25(OH)-vitamin D) levels in PCa patients. Blood samples were collected from 111 PCa patients and 150 age-matched healthy volunteers. The VDR rs2228570 T/C, rs1544410 G/A, and VDBP rs7041 T/G genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). 25(OH)-vitamin D and PSA (Total and Free) serum levels were measured. The frequencies of VDBP genotypes T/G vs. T/T (56.5% vs. 44.5%, p = 0.01) according to the dominant model T/G + G/G vs. T/T (84.3% vs. 71.5%, p = 0.01) were significantly higher in PCa patients when compared to control group and considerably increased the risk of disease by 2.29, 1.44, and 2.13 folds respectively. Interestingly, the results demonstrated that PCa patients with the dominant model (T/G + G/G vs. T/T) of VDBP had significantly lower serum levels of vitamin D and higher serum levels of total and free PSA in comparison to the controls. Furthermore, when compared to controls, PCa patients with the dominant model T allele (T/G + G/G vs. TT) of VDBP had significantly higher vitamin D, total PSA, and free PSA concentrations. Serum levels of 25(OH)-vitamin D and rs7041 T/G polymorphism of the VDBP gene could be potential risk factors for PCa.

The application of Tarkhineh texture to protect probiotics in potato chips has been investigated as the main goal in this paper. In this study, the probiotic assessments, morphological characteristics, sensory evaluation, and survival rates of the covered probiotic cells with Tarkhineh in potato chips during storage time were assessed. Based on results, T34 isolated from traditional Tarkhineh as a safe strain had a high tolerance to low pH and bile salt conditions, displayed acceptable anti-pathogenic activities, and also showed desirable antibiotic susceptibility. Two types of Tarkhineh formulations (plain Tarkhineh and turmeric Tarkhineh) were applied using a simple spraying method for covering T34 cells in potato chips. All formulations showed elliptical to spherical (480-770 μm) shape probiotic drops. Storage stability results revealed that T34 cells mixed with turmeric and plain Tarkhineh during 4 months of storage at 4°C displayed excellent protection abilities with about 3.70 and 2.85 log decreases in CFU/g respectively. Additionally, probiotic potato chips compared to non-probiotic and commercial potato chips, exhibited probiotic product criteria such as excellent quality and superior sensory properties during storage time. In conclusion, Tarkhineh showed high potential as a protective matrix for probiotic cells in potato chips.

We investigated the association between p16 expression and histopathologic parameters including size, neural and vascular invasion, and lymph node involvement in breast cancer. 58 specimens from patients with different grades of breast cancer were included. Hematoxylin and eosin and immunohistochemistry staining for p16 was performed. 5 patients (8.6%) had grade I, 23 (39.7%) had grade II, and 30 (51.7%) had grade III breast cancer. Assessment of the tumor size showed that 5 (8.6%) tumors had a size of ≤2cm, 29 (50%) were between 2-5 cm and 24 (41.4%) had a size of ≥5cm. Moreover, 45 (77.6%) of the included patients had axillary lymph node involvement. Investigation of association between p16 positivity with pathological parameters in three groups with positivity to p16 (1-25%, 26-75%, >75%) showed that there was no association between p16 positivity and other parameters including histologic score (p=0.44), tumor size (p=0.77), neural invasion (p=0.79), perivascular invasion (p=0.98) and the number of involved LNs (p=0.49). From the group including eight patients with >75% p16 positivity, seven (87.5%) were found with neural invasion and two (25%) with perivascular invasion. P16 positivity was not associated with size, neural and vascular invasion, and LN involvement in breast cancer., Competing Interests: The authors declare that they have no conflicts of interest.