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This review examines the impact of F420 biosynthesis protein C (fbiC) mutations in Mycobacterium tuberculosis (Mtb) and their influence on the bacterium’s dormancy mechanisms. The potential role of fbiC mutations and functional impairments in the persistence of Mtb is emphasized. Tuberculosis (TB) bacilli can enter a dormant state with minimal metabolic activity, allowing them to conserve resources and survive in low-nutrient, low-oxygen environments for extended periods. While the fbiC gene contributes to dormancy, Mtb can achieve this state through multiple genetic and metabolic pathways, suggesting that it may still undergo dormancy even with functional impairments in fbiC. In this review, we utilized several scientific databases, including PubMed, Web of Science, and Google Scholar, and set of key search terms including “fbiC gene,” “F420 Biosynthesis,” “Mycobacterium tuberculosis,” “Dormancy,” and “Drug Resistance” to highlight the significance of the fbiC gene in regulating dormancy and explore how Mtb compensates for fbiC dysfunction through various metabolic adaptations.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), can enter a dormant phase within host tissues, complicating treatment and highlighting the need to investigate the genetic changes associated with dormancy. Methods: This study examined clinical isolates of MTB, representing a range of susceptibility profiles and standard reference laboratory strains, i.e., H37Rv and Mycobacterium bovis bacillus Calmette–Guérin. Each strain was subcultured in a controlled laboratory environment to analyze two distinct phases: one maintained in vitro under a double-stress dormancy model using the Wayne model (characterized by the absence of oxygen and nutrients) for 12 months, and the other examined during its exponential growth phase. Whole-genome sequencing and protein structure analysis using bioinformatics tools were performed to characterize and compare mutations in isolates at each phase. Results: Three distinct frameshift mutations were identified in the fbiC, PPE35, and ald genes, and one upstream mutation in whiB6 genes in all studied isolates under dormancy, irrespective of their susceptibility patterns (P < 0.01). Among drug-resistant strains, at the exponential phase isolated from patients with prolonged treatment, 5%–7% had PPE35, ald mutations, whereas 95% had the whiB6 mutation, suggesting that adaptive stress responses may be triggered under in vivo conditions. Conclusions: The newly identified frameshift mutations (fbiC, PPE35, and ald genes), consistently found in both laboratory and clinical isolates, seem to play a critical role in the survival of MTB during dormancy. Based on these findings, designing a molecular test to differentiate between active and latent TB possibly enables timely prophylactic interventions.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious threat to global tuberculosis (TB) control efforts. This study aims to investigate the trend of MDR-TB prevalence in Iran over 20 years. Methods: A systematic literature search was conducted in various databases, including PubMed, Embase, and Web of Science, from 1981 to 2023. Studies reporting the prevalence of MDR-TB in Iran were included in the meta-analysis. Statistical analysis was performed using Comprehensive Meta-Analysis software. Results: A total of 58 studies from different provinces of Iran were included in the meta-analysis. The majority of studies were from Tehran (n = 33), Kermanshah (n = 5), Mashhad (n = 4), and Tabriz (n = 4) provinces. Overall, 1885 cases of MDR-TB were reported in Iran during the study period. The highest number of MDR-TB cases was reported in 2000 (582 cases) and the lowest in 2001 (1 case). An increasing trend in MDR-TB prevalence was observed, particularly between 2018 and 2019. The pooled prevalence of MDR-TB in Iran was 12.31% (95% CI: 11.83–12.80) using the fixed-effects model and 20.21% (95% CI: 15.70–26.01) using the random-effects model. No evidence of publication bias was found. Conclusion: The results of this comprehensive meta-analysis highlight the increasing trend of MDR-TB in Iran over the past two decades. This underscores the urgent need for strengthening TB control strategies, including improved surveillance, case detection, treatment, and management of MDR-TB in the country. Developing diagnostic and treatment approaches for MDR-TB should be prioritized by Iranian medical universities and public health authorities.

Background: Pharmacogenetic research has led to significant progress in understanding how genetic factors influence drug response in tuberculosis (TB) treatment. One ongoing challenge is the variable occurrence of adverse drug reactions in some TB patients. Previous studies have indicated that genetic variations in the N-acetyltransferase 2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) genes can impact the blood concentrations of the first-line anti-TB drugs isoniazid (INH) and rifampicin (RIF), respectively. This study aimed to investigate the influence of pharmacogenetic markers in the NAT2 and SLCO1B1 genes on TB treatment outcomes using whole-exome sequencing (WES) analysis. Methods: DNA samples were collected from 30 healthy Iranian adults aged 18–40 years. The allelic frequencies of single-nucleotide polymorphisms (SNPs) in the NAT2 and SLCO1B1 genes were determined through WES. Results: Seven frequent SNPs were identified in the NAT2 gene (rs1041983, rs1801280, rs1799929, rs1799930, rs1208, rs1799931, rs2552), along with 16 frequent SNPs in the SLCO1B1 gene (rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs2291075, rs201722521, rs11045852, rs11045854, rs756393362, rs11045859, rs74064211, rs201556175, rs34671512, rs71581985, rs4149085). Conclusion: Genetic variations in NAT2 and SLCO1B1 can affect the metabolism of INH and RIF, respectively. A better understanding of the pharmacogenetic profile in the study population may facilitate the design of more personalized and effective TB treatment strategies. Further research is needed to directly correlate these genetic markers with clinical outcomes in TB patients.

Background: Endophytic fungi live inside the plant tissue, and can produce bioactive compounds. Methods: Herein, the molecular identification, phenols metabolites analysis, and biological properties (enzymatic and antioxidant) of endophytic fungi isolated from the aerial parts of Tragopogon graminifolius were studied. The enzyme produced by endophytic fungi was tested by the formation of a clear zone/pink around the colonies. The 2, 2-diphenyl-1-picrylhydrazyl method was used for the investigation antioxidant properties of isolated fungi. Moreover, the total flavonoid and phenol contents were studied using aluminum chloride colorimetric and Folin–Ciocalteu methods, respectively. Furthermore, the phenolic acids analysis was performed using high-performance liquid chromatography. Results: In this study, two isolates were identified (Talaromyces amestolkiae and Rhizopus oryzae). Evaluation of the enzymatic activities indicated that R. oryzae had the ability to produce amylase and pectinase, whereas T. amestolkiae exhibited extracellular activity for amylase, L-asparaginase, and pectinase. The result of the antioxidant property study indicated that T. amestolkiae had the highest antioxidant property and its IC50 value was 617 μg/mL. Moreover, these fungi had the highest flavonoids and phenols amounts. The phenolic acid analysis indicated that m-coumaric acid was the major phenolic acid which was determined by the studied fungi. Conclusion: This report was the first study of endophytic fungi from T. graminifolius, and the outcome of this study can be a way to produce m-coumaric acid at an industrial scale.

Abstract Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

Abstract Cancer is a complex disease with many contributing factors, and researchers have gained extensive knowledge that has helped them understand the diverse and varied nature of cancer. The altered patterns of DNA methylation found in numerous types of cancer imply that they may play a part in the disease’s progression. The human cancer condition involves dysregulation of the DNA methyltransferase 3 beta (DNMT3B) gene, a prominent de novo DNA methyltransferase, and its abnormal behavior serves as an indicator for tumor prognosis and staging. The expression of non-coding RNAs (ncRNAs), which include microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), is critical in controlling targeted gene expression and protein translation and their dysregulation correlates with the onset of tumors. NcRNAs dysregulation of is a critical factor that influences the modulation of several cellular characteristics in cancerous cells. These characteristics include but are not limited to, drug responsiveness, angiogenesis, metastasis, apoptosis, proliferation, and properties of tumor stem cell. The reciprocal regulation of ncRNAs and DNMT3B can act in synergy to influence the destiny of tumor cells. Thus, a critical avenue for advancing cancer prevention and treatment is an inquiry into the interplay between DNMT3B and ncRNAs. In this review, we present a comprehensive overview of the ncRNAs/DNMT3B axis in cancer pathogenesis. This brings about valuable insights into the intricate mechanisms of tumorigenesis and provides a foundation for developing effective therapeutic interventions.

Abstract MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate the expression of target genes post-transcriptionally and interact with mRNA-coding genes. MiRNAs play vital roles in many biological functions, and abnormal miRNA expression has been linked to various illnesses, including cancer. Among the miRNAs, miR-122, miR-206, miR-21, miR-210, miR-223, and miR-424 have been extensively studied in various cancers. Although research in miRNAs has grown considerably over the last decade, much is yet to be discovered, especially regarding their role in cancer therapies. Several kinds of cancer have been linked to dysregulation and abnormal expression of miR-122, indicating that miR-122 may serve as a diagnostic and/or prognostic biomarker for human cancer. Consequently, in this review literature, miR-122 has been analyzed in numerous cancer types to sort out the function of cancer cells miR-122 and enhance patient response to standard therapy.

Background: Immune responses may be involved in the development of pseudoexfoliation (PEX), pseudoexfoliation glaucoma (PEXG), and primary open-angle glaucoma (POAG) pathogenesis. The aim of the present study was to evaluate the association of IL12B rs3212227 A/C and INFG rs1861494 T/C polymorphisms with the risk of PEX, PEXG, and POAG in an Iranian population. Methods: Totally, 55 POAG, 57 PEX, and 78 PEXG patient cases as well as 79 healthy controls were included in this study. Genotyping of the IL12B and INFG polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism methods using TaqI and FauI restriction enzyme, respectively. Results: Results indicated that IL12B AC genotype was significantly higher in POAG (36.4%; P < 0.001; odds ratio [OR] = 4.0, 95% confidence interval [CI]: 1.7–10.0) and PEX patients (36.4%; P = 0.023; OR = 2.7, 95% CI: 1.1–6.9) compared to the control group (12.6%). The C allele could be considered a risk factor for POAG (P = 0.002; OR = 3.1, 95% CI: 3.1–6.8) and PEX (P < 0.001; OR = 3.4, 95% CI: 3.4–7.3). INFG TC genotype was significantly higher in PEX (38.6%; P = 0.007; OR = 2.8, 95% CI: 1.3–6.3) and PEXG patients (37.2%; P = 0.009; OR = 2.7, 95% CI: 1.1–6.9) compared to the control group (19.0%). The C allele seemed to be a risk factor for PEX (P = 0.002; OR = 2.8, 95% CI: 1.4–5.7) and PEXG (P = 0.009; OR = 2.4, 95% CI: 1.2–4.7). Conclusion: Overall, IL12B was associated with susceptibility to POAG and PEX, and IL12B C allele increased the risk of POAG and PEX. In addition, INFG was associated with susceptibility to PEX and PEXG, and the INFG C allele seemed to be a risk factor for PEX and PEXG.

Background: Proline-glutamate (PE)/proline-PE (PPE) proteins play an important role in the development of mycobacterial pathogenicity by modulating the host immune system. In the present investigation, the structural changes in PE-polymorphic GC-rich sequences (PGRS) family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) were compared and analyzed in exponential state and under in vitro model of latency in same clinical isolates of Mycobacterium tuberculosis (MTB). Methods: MTB strains were isolated from clinically and laboratory-confirmed cases of tuberculosis (TB). The TB isolates were subjected to the Xpert MTB/rifampin test and then, further susceptibility testing using proportional methods was performed on them. The isolates were characterized using both 16S–23S RNA and hsp65 genes spacer polymerase chain reaction-restriction fragment length polymorphism. Selected isolates studied at two experimental set–up at exponential phase OD 600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition for 26 months to selected isolates studied at two experimental setup in exponential phase OD600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition after 26 months. Whole-genome sequencing was performed on studied isolates and the protein structures were analyzed using a bioinformatics web server. Results: No deletion, insertion, or substation occurred in susceptible, mono-drug and multidrug resistant-TB isolates were observed at PE-PGRS family protein Wag22 (Rv1759c) and PE_PGRS31 (Rv1768) at exponential phase. Although, a large deletion (at Rv1759c; Rv1768) was observed in extensively drug-resistant (XDR) and totally drug-resistant (TDR) TB isolates at the exponential phase. All studied TDR-TB isolates had a common deletion position from amino acid 1 (methionine) to amino acid 83 (glycine) and from amino acid 725 (proline) to amino acid 914 (threonine) at PE-PGRS family protein Wag22 (Rv1759c). At PE_PGRS32 (Rv1803), deletion occurred from amino acid 1 (methionine) to amino acid 212 (glycine) in latent TDR-TB bacilli. No changes in Rv1803 were observed in other studied isolates. In contrast, 66.6% of studied isolates had either insertion, deletion, substitution, or combination of changes at PE_PGRS33 (Rv1818c). However, the majority of changes at Rv1818c occurred in drug-resistant isolates. We also documented the region of deletion and insertion at PE_PGRS33 (Rv1818c) is different in active and latent TDR-TB isolates. Conclusions: Changes in these PE-PGRS family protein was associated with drug susceptibility patterns of individual isolates. Our result showed a total frameshift mutation of protein that had a different length in comparison to the original protein. These changes might disturb the interactions between XDR and TDR-TB isolates and immune responses, which needs further investigation.

Background: Telemedicine has been used for cystic fibrosis (CF) in a wide range of signs and symptoms even before the COVID 19 pandemic, however, little is known about the health consequences and use of specific health care for cystic CF. This study aimed to evaluate the evolution of clinical trends and data related to mobile based monitoring activities in CF patients at home for 3 years. Methods: This is a semi experimental single group study. Forty five CF patients under 7 years' old who were referred to the Masih Daneshvari Hospital between 2018 and 2021 were selected. A mobile phone_based customized Short Message Service (SMS) application used to monitor patients. Remotely monitored variables included the amount and color of sputum, cough, wheezing, and shortness of breath at rest. SPSS using Chi square and Friedman tests. Results: The condition of patients based on the number and type of cough increased sputum, decreased appetite, fatty stool, fever and dyspnea, headache, noninvasive ventilation, and drug comfortably remained almost unchanged in the study of the 1st, 2nd, and 3rd years, and the studied parameters did not show a significant difference (P > 0.05). Of course, the number of outpatient visits decreased significantly (P value: 0.02). The respiratory rate and arterial oxygen saturation variables were almost the same in three consecutive annual measurements (P values: 0.544 and 0.639, respectively). Conclusion: Telemedicine is a method that is useful in the follow up of chronic diseases such as CF and improves the quality of life and reduces the deterioration of lung function; therefore, there is less need for invasive treatments in the long run, and a fundamental change in referral motivation brings to the hospital.

Background: The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position −56 was assessed in PPD plus group before and after COVID-19 infection (2017–2018; 2020–2021). Methods: The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5–10 years) with PPD positivity >15 mm (16–20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017–2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (−56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. Results: In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26–1.83, and P = 0.46). Although in position −56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78–0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23–2.86, and P = 0.75), whereas the dominate allele at position −56 was T in Group A (OR = 1.37, 95% CI, 0.62–3.02, and P = 0.42). Conclusion: No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (−56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018–December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein–Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018–2019 and 5220 specimens (30.8%; from 2175 patients) in 2020–2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Background: Pili producing genes in different life cycles of Mycobacterium tuberculosis (M. tuberculosis) were assessed. M. tuberculosis has two life cycles: dormant and active states. We aimed to assess the pili producing genes such as curli pili of M. tuberculosis (mtp) encoded by the mtp gene (Rv3312A) and fimbrial low-molecular-weight protein encoded by flp gene (Rv3656c) which were compared and analyzed. Methods: Two hundred M. tuberculosis isolates were investigated both at active and dormant states for production and expression of pili. The dormant M. tuberculosis was achieved by incubation in a sealed tube (modified Wayne method). The susceptibility of M. tuberculosis was evaluated on genes, rpob, inh, katg, and gyra by using multiplex polymerase chain reaction (PCR) and single-strand conformational polymorphism methods. The PCR–restriction fragment length polymorphism was used to express pili genes mtp and flp and then the PCR products was digested using restriction enzyme Fnu4HI, XmaI, and MspJI and AciI, TagII, and HaeII, respectively. The transmission electron microscopy was also used to detect pili in different isolates. The result was compared and analyzed using H37RV as a gold standard. Results: The mtp and flp PCR products were 263 and 122 bp in the studied strains irrespective of M. tuberculosis different life cycles, respectively. The PCR products were analyzed on 8% Polyacrylamide gel electrophoresis (PAGE), and in the 180/200 (20%), producing five fragments of 25,40,45,63,90 bp with the Fun4HI and two fragments of 126,138 bp with the XmaI and uncut with the MspJI for mtp gen were obtained at the dormant and active states of M. tuberculosis (P < 0.05). Similarly in flp gene producing three fragments of 22,35,65 bp with AciI and two fragments of 35.87 bp with TagII and two fragments of 38.84 bp with HaeII were obtained (P < 0.05). In contrast to genotyping analysis, the electron microscopy examination showed protruding of pili from M. tuberculosis, especially in dormant mycobacterium (15/100; 15%), that was multidrug resistance and extensive drug resistance isolates (P > 0.05). Conclusion: Pili were shown by electron microscopy, although at the gene expression, the insignificant difference was observed at the dormant strains in comparison to active states. Therefore, we may conclude that other genes might be involved in pili production of M. tuberculosis that needs further investigation. Although, the resistance phenomena might influence the pili producing gene expression that showed in our results.

Background: Nowadays, ionic polymer–metal composites are widely used in various industries. They are in the group of electroactive polymers and smart materials with electromechanical properties. By applying a small amount of voltage, the nonlinear stress inside them will happen and their deformation can be seen. The energy transformation from electrical to mechanical is observable during the process of giving voltage to a specimen. The aim of this study is to investigate a novel experimental static deflection equation for specific cantilever beam made of ionic polymer–metal composite. Methods: In this paper, an ionic-polymer-metal composite is provided; the main core is based on an electroactive Fluoropolymer named Nafion, and the coated electrodes are made of Platinum. The length of the specimen is 27.131 mm and its width is 5.728mm. Voltage from 1.5 to 4.3V was applied to the specimen used in this study; the y-directional displacement of the IPMC at each step is measured and recorded; then, a finite element analysis was performed. Curve fitting of the data for the experimental analysis was also done. Moreover, the governing relations of IPMC according to the Nernst–Planck equation were investigated in this study. Results: The results have been validated in two forms of finite element method and experimental analysis. The results of finite element analysis showed that the ion flux in the polymer is calculated by the equation: [INSIDE:1]. In other words, this equation, which is called Nernst–Planck, is the basic equation of this type of material. This equation is the main governing equation to describe the transfer phenomena of IPMC materials. Furthermore, in order to calculate the deflection of IPMC membrane, 19 equations designed in this study were used. In the next step, the results of the experimental analysis showed that, based on the field emission scanning electron microscope images, the Nafion surface is completely sandblasted and its area is completely uniform. The right image taken by Dino-Lite shows the thesis effect on the electrode. Furthermore, the results showed that IPMC has high-quality coated electrodes. Conclusions: It is shown that a nonlinear equation governs the behavior of IPMCs' deflection versus voltage.

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) remain the leading causes of lung disease and mortality worldwide. Interferon-gamma (IFN-γ) and its receptor (IFN-γR) play a key role in mediating immunity against Mtb and NTM. This study was conducted as a systematic review; all information was collected from databases such as: PubMed, Scopus, Medline, SID, and medical databases. Finally, all the collected data were reviewed, and all content was categorized briefly. There is growing evidence that IFN-γ plays an important role in host defense against these two intracellular pathogens by activating macrophages. In addition, IFN-γ has been shown to be an integral part of various antibacterial methods such as granuloma formation and phagosome-lysosome fusion, both of which lead to the death of intracellular Mycobacterium. As a result, its absence is associated with overgrowth of intracellular pathogens and disease caused by Mtb or Mycobacterium nontuberculosis. We also look at the role of IFN-γR in Mtb or NTM because IFN-γ acts through IFN-γR. Finally, we introduce new approaches to the treatment of M. tuberculosis complex (MTC) and NTM disease, such as cell and gene-based therapies that work by modulating IFN-γ and IFN-γR.

Background: Salsola vermiculata is an annual plant which is broadly distributed in southwest of Asia. Due to the lack of data regarding the biological properties of different parts of S. vermiculata, the present research focused on their biological activities. Methods: Different parts of plant were harvested, and phytochemical assay of S. vermiculata parts was performed to determine the presence of phenols, flavonoids, alkaloids, fixed oils, and volatile oils. Then, their antioxidant and cytotoxicity activities of the extracts and fractions were evaluated according to DPPH and MTT assay, respectively. Furthermore, the antimicrobial activities of the extracts and fractions were determined by the disk diffusion and minimum inhibitory concentration methods. Results: According to the results, the antioxidant activity and the phenolic contents in leaves and flowers crude extracts of S. vermiculata were high, and their ethyl acetate fractions had higher activities compared to other fractions. The cytotoxic study indicated that the seeds and roots crude extracts significantly exhibited cytotoxic activities with IC50 values of 33.88, 42.92 μg/mL, respectively, and only the fixed oil fractions had cytotoxic activity. Antibacterial activity showed that the fixed oil fraction of roots had the highest activity against Staphylococcus aureus, followed by fixed oil fraction of seeds and volatile oil fraction of the roots. Conclusions: Different parts and fractions of S. vermiculata contain various bioactive compounds with different biological activities, and the results of this study could provide useful information to guide the application of S. vermiculata parts in food and pharmaceutical fields.

Mycobacterium tuberculosis has infected more than two billion individuals worldwide, of whom 5%–10% have clinically active disease and 90%–95% remain in the latent stage with a reservoir of viable bacteria in the macrophages for extended periods of time. The tubercle bacilli at this stage are usually called dormant, non-viable, and/or non-culturable microorganisms. The patients with latent bacilli will not have clinical pictures and are not infectious. The infections in about 2%–23% of the patients with latent status become reactivated for various reasons such as cancer, human immunodeficiency virus infection, diabetes, and/or aging. Many studies have examined the mechanisms involved in the latent state of Mycobacterium and showed that latency modified the expression of many genes. Therefore, several mechanisms will change in this bacterium. Hence, this study aimed to briefly examine the genes involved in the latent state as well as the changes that are caused by Mycobacterium tuberculosis. The study also evaluated the relationship between the functions of these genes.

Objective: To investigate the prevalence of non-tuberculosis mycobacteria (NTM) among the samples deposited from the National Tuberculosis Reference Laboratory of Iran between 2011 and 2018. Methods: The study evaluated the prevalence of NTM among specimens from patients with pulmonary tuberculosis symptoms (n=15 771) deposited at the National Tuberculosis Reference Laboratory of Iran from 2011 to 2018. Detection of Mycobacterium (M.) tuberculosis was based on presence of a 190-bp amplicon from IS6110 insertion sequence using Tb1 and Tb2 primers, and amplicon-negative specimens were tested for NTM and M. tuberculosis (refractory to IS6110 amplification) using restriction fragment length polymorphism PCR of hsp65 amplicon fragment. Results: A total of 7 307 (46.33%) M. tuberculosis and 658 (4.17%) NTM specimens were found, the latter mainly comprising M. abscessus (10.18%), M. avium (2.28%), M. chelonae (8.97%), M. intracellulare (10.49%), M. kansasii (4.71%), and M. simiae (56.08%). Conclusions: As treatment for NTM differs from that for M. tuberculosis, accurate detection of Mycobacterium sp. is of public health significance.

Abstract Background The involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms −592C/A (rs1800872), − 819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG). Methods In this study, 114 PEX, 118 PEXG, 114 POAG patients and 126 healthy individuals from Iranian population were participated. Detailed ophthalmic examinations by an ophthalmologist including slit-lamp bio-microscopic examination, dilated examination of the lens, gonioscopy, and funduscopy were carried out on patients and controls. Genomic DNA was extracted from the blood samples and ARMS–PCR was performed to detect promoter polymorphisms of IL-10. Results In all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of −819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX (P = 0.02, OR = 5.76, 95% CI = 5.17–24.49), PEXG (P = 0.006, OR = 7.54, 95% CI = 6.62–30.76) and POAG (P = 0.003, OR = 8.11, 95% CI = 7.13–33.15). Conclusions Our results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

In December 2019, there was an outbreak of pneumonia with an unknown cause in Wuhan, Hubei province, China. Within less than 3–4 months, the virus has spread to more than 200 countries. The virus rapidly transmitted from different places of the world with various cultural traditions. Thereby, the question is remained to be resolved about the main intermediate carrier of diseases in different animals. Studied showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originated from horseshoe bats, but its intermediate hosts are still largely unknown. Therefore, the possibility of horseshoe bat infection by ticks is high during the flight between plants or when resting in these places. Female ticks can either feed on horseshoe bat blood for 5–7 days before shedding or can form large aggregations by laying several thousand eggs in the right places or on them. Once they feed on horseshoe bat blood containing SARS-CoV-2, they can transfer the infection to the next generations without the need to reuse infections from the reservoir host. With all the potential features that this creature has, it is mandatory to investigate the presence or absences of SARS-CoV-2, especially when we know that ticks co-exist with that horseshoe bats. These factors highlight the importance of studying the viral epidemiology in the tick population. Thereby, based on the wide distribution of ticks and their co-existence with horseshoe bat, we suggest further studies on ticks that might act as one of the main intermediate hosts in different animals.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes the COVID-19 infectious disease. Despite the high level of quarantine control in many well-developed countries, the disease has spread to more than 113 countries all over the world, creating a global pandemic. This emerging situation raises many questions. Can the infection be just through human-to-human transmission or are other sources, for example, animal to human or other environmental sources, also involved? We reviewed the previous literature and assessed the potential risk of transmitting the coronavirus from pets to humans. The pets (dogs and cats), especially dogs, have a habit of licking themselves in the buttocks, or smelling others in the buttocks. In such a way, they may get the virus into their respiratory or digestive tract. In return, once they lick people in the face, they may transmit the diseases. In this study, we not only reviewed the literature on pets and their relationship to the coronavirus but we also tested 22 stray dogs and cats, collected from nearby areas that were used for hospitalization of COVID-19 patients. Although no direct connection was found between these pets and the hospital, we found that 14 (63.6%) out of the 22 pets were positive for COVID-19 with the molecular test. Among them, seven (31.8%) had coughing and sneezing symptoms. The studied cases were stray pets, but the question that remains to be clarified is whether home pets are engaged in a chain of transmission or not? This needs further investigation.

Tuberculosis (TB), especially in developing countries, is a major threat to human health. The pathogenesis of TB remains poorly understood, and

Coronavirus (COVID-19), a type of RNA virus, has a positive, single, sense stranded RNA. Studies of coronaviruses have shown high mutations in the virus's RNA. The more the virus infects people, the more the genome will mutate. In addition, evolutionary and genetic studies have the potential to recombine and easily jump from one host to another host. This means flexibility to adapt to new conditions and proliferation in new host cells. Examination of the hosts of this virus shows their extent. Studies show that the virus closely resembles hosts such as bats and pangolins. Genomic studies on severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and bat coronavirus (RaTG13) showed 96.2% genetic similarity although there are differences in the nucleotides of different hosts. The importance of examining mutated areas in coronaviruses for diagnosis and treatment is necessary because molecular methods such as RT-PCR, although having a specific probe, may not cause a connection between the primer and the specific probe and cause a false-negative response be reported. This issue has led various countries to sequence SARS-CoV-2 for their own countries, eventually leading to the identification of specific drugs and vaccines for their country.

Background: Cold plasma is shown to inhibit the cancer cell growth. Manipulation of different plasma parameters might have influence on the production of major reactive species which leads to killing of the cancer cells. Antiproliferative activity of cold atmospheric pressure plasma jet was investigated on small-cell lung carcinoma BHY cell line (squamous cell carcinoma) under different in vitro conditions. Methods: A homemade plasma jet was designed and created using pure helium gas. To identify the species created by the plasma jet, optical emission spectroscopy (OES) was employed. Next, the effect of plasma jet was examined on lung cancer cell survival by MTT assay and the effects of main parameters were evaluated on plasma performance. In this favor, various treatment times including 60, 90, 120, 180, and 300 s in combination with different voltages of 5, 11, and 14 kV were investigated, and the results were analyzed at 2, 24, and 48 h after exposure to plasma. Results: Predominant species of OES spectra were O, OH, N2+, and N2. Results of MTT assay indicated a dramatic reduction in cell viabilities in both dose- and time-dependent manners, and more than 75% of cancer cells were died after 48 h at 180 s of plasma treatment. Conclusion: The homemade plasma jet can chiefly contribute to the production of reactive oxygen and nitrogen species (reactive oxygen species and reactive nitrogen species) and can induce apoptosis in small-cell lung carcinoma BHY cell line.

Tuberculosis is a highly infectious illness that has been considered a worldwide health danger. Existence inside macrophages is a main characteristic of Mycobacterium tuberculosis virulence and essential to make a perdurable infection in the human body. Recently, a pivotal cytotoxicity determinant of M. tuberculosis in macrophages was discovered and named channel protein with necrosis-inducing toxin (CpnT). CpnT includes an N-terminal channel domain and a C-terminal domain (CTD). The CTD is a secreted toxin and can induce a necrotizing process in the macrophages. The CTD has strong nicotinamide adenine dinucleotide (NAD+)-glycohydrolase activity that empties NAD+ reservoirs of cells, resulting in human cell necrosis. In this study, the structural and functional properties of the CTD were reviewed. Besides, to predict local similarity between the CTD and other protein sequences and infer the functional and evolutionary relationships, the Basic Local Alignment Search Tool was used. Several protein sequences of the Mycobacterium showed >50% similarity to the CTD, indicating species specificity of the CTD. However, some prokaryotic and eukaryotic sequences showed 20%–45% similarity to the CTD, indicating that the CTD belongs to an uncharacterized protein family including nonbacterial proteins.

Bacteria show a plenty of cellular shapes and can alter their forms. The bacterial cell shape is functionally important. Bacteria have a number of options to select their shapes in order to uptake more nutrient, motility, attachment to surface, symmetrical division of chromosomal elements, and localization of complex secretion apparatuses. Some factors including peptidoglycan and cytoskeleton-like proteins can regulate and keep the bacterial shape. In the case of Mycobacterium tuberculosis, the reported morphological variation in the pathogen are classified into two categories; those which frequently seen at exponential phase of growth that is rod, V, Y-shape, branched, or buds, and those that are seen occasionally under stress or environmental conditions which are round, oval, ultra-virus, spore-like, and cell wall defiant or L-forms. Growth conditions and age of the cells can influence on the shape and size of the pathogen in a range from coccobacilli to long rods. Under unsuitable conditions including starvation or oxygen deprivation, tubercle bacillus assumed a swollen shape without making the vacuolar or globoid bodies. The physical circumstances and nutritional feature will control the temporary lifestyle of the pathogen.

Background: Mycobacterium farcinogenes and Mycobacterium senegalense are the causes of the bovine farcy, a chronic granulomatous disease of the skin of zebu cattle. The zoonotic potential of these bacteria is unclear. The high contamination rate of these bacteria (as species of nontuberculous mycobacteria) has been reported in environmental samples. This study aimed to determine the prevalence of these bacteria in the water and soil environment in four suburbs of Tehran, Iran. Methods: A total of 4014 soil and water samples were collected from four areas of Tehran including Robat Karim, Firuzkuh, Shahr-e-Ray, and Varamin. In each city, at least one sample was collected per 1002 m. The sediment samples were cultured on the Lowenstein–Jensen medium. Twice a week was observed to study the growth of colony, morphology, and pigmentation. Colonies were studied using phenotypic tests. Molecular analysis was also carried out on colonies. Results: Among samples, the number of collected water samples was 48.48% (1946/4014), and the number of soil samples was 51.51% (2068/4014). Results of cultures from collected samples showed that 21.47% (862/4014) of them were positive. Among the studied areas, Rabat Karim has been identified as the most polluted region (169/480; 35%). The abundance of M. farcinogenes has been dominant in Ray. The least infection has been reported in Varamin. Conclusion: The results showed that the prevalence of these two strains was very high in water and soil. Due to these two strains are the main and effective factors of bovine farcy in zebu cattle (the most farmed cows in Iran), surveillance of the zoning potential of this disease is very important.

Background : Daily intake of air is 30 Ib as compared with 2-Ib of food and 4½ of water. Thereby, breathing-contaminated air is as harmful as drinking or eating contaminated water or food, respectively. Recent research has highlighted the extent of outdoor air pollution in large cities and warranted high-quality studies to clarify the magnitude of the problem. Here, we evaluated the possible association between tuberculosis (TB) development and exposure to outdoor air pollution in a metropolitan city of Tehran. Methods: Extraction and analysis of relevant data. Investigation performed on TB patients (n = 1167) that were residing in Tehran for the past 10 years. The average concentration of sulfur dioxide (SO2), nitrogen dioxide, carbon monoxide (CO), and particles with an aerodynamic diameter of ≤ 2.5μm (PM2.5) and ≤ 10.0 (PM10) was measured from Tehran Air Quality Control Corporation (TAQCC). Patient and ecological informations were analyzed using geographical information system. Results: Based on TAQCC, Tehran had an average of 180–250 polluted days per year for the last 10 years. The high incidence of pulmonary TB (18 to 31/100,000) was detected in populations which were exposed to high concentration of CO (2.7 to 5.2 parts per million, 95% confidence interval [CI]; 1.10 to 1.90) and PM2.5(35 to 42μg/m3; 95% CI 1.03 to 1.80). The level of SO2,NO, and PM10was also high but not significantly related to TB (P > 0.05). Conclusion: The long-term exposure to PM2.5 and CO was positively associated with TB development.

Cystic fibrosis (CF) has been generally well defined throughout the world although its prevalence is very difficult to ascertain for a number of reasons, including the fact that the medical/scientific literature and patient registries vary in quality in different countries. In the present review literature (1938–2017), we found out the higher frequency of registered CF patients in the European Union. This could be due to strong clinical awareness and greater health facilities. In contrast, we found a very irregular report from Asian and African countries. In these countries, the national CF registration system is mostly lacking or it is individualized-based research. In this situation, the estimation of various risk factors such as ethnicity and/or races is remained to be resolved. Overall, this review outlines the urgent need for revitalization of national and global CF registration, worldwide.

Backgrand: For patients with long segment of tracheal stenosis, resection and replacement is necessary. Tracheal reconstruction associated with complications such as stenosis, insufficiency of blood supply and surgical complication. Methods: In this study, we prepared collagen-chitosan scaffold and sheep's decellularized trachea plus culture medium with nanocup contain growth factors for chondrocyte and fibroblast-epithelial cell culture in rotary bioreactor. After attachment of cells, engineered trachea put into the omentum. Peritoneal stem cell interact with the epithelial and chondrocytes with attendance of growth factors released from nanocup. The bioengineered trachea with omental pedicle transposed from behind the sternum and transplanted in the position of resected trachea. In third experiment, we introduce the in situ tracheal repair technique with injectable matrix for reconstruction of long-segmental stenosis of trachea in a 29-year-old woman. Results: Severe tortuosity in the first experiment and mild stenosis was seen in the second experiment. In third experiment, normal shape in tracheal diameter was seen at injection sites. The interior portion of the trachea at virtual computed tomography (CT) scan and bronchoscopy were similarity to normal after four month fallowing up of injection. Conclusions: Severe tortuosity, mild stenosis in whole length of trachea in this study and disadvantage of trachea transplantation include open surgery, fatal consequences of anastomosis leakage, and rupture besides large mediastinal vessels; hence, we decided to introduce the novel in situ tracheal repair technique. Injectable bioresorbable scaffolds may be used as a temporary scaffolding for transplanted cells and thereby allow the cells to secrete extracellular matrix of their own to enable, in the long term, a complete and natural tissue replacement.

Background: Recent advances in nanotechnology-based drug delivery system have been shown to improve either antibacterial efficacy or pharmacokinetics behavior.The aim of this study was to design a rifampin nanoparticle (RIF-NP) which has a high loading capacity with the slow release profile. Material and Methods: The designed chitosan/gelatin/lecithin (Chg/L) RIF-NPs were prepared by multilamellar vesicle. Thereafter, the particle size, zeta potential, morphology, and release rate were investigated. To optimize the loading capacity and release profiles, different concentrations of lecithin were used. Results: Our results showed a correlation of lecithin concentration with size, zeta potential, and loading capacity of RIF-NPs. Increases in lecithin concentration (0.2–2.0 g) could cause a significant size reduction in NPs (250–150 nm); the amount of zeta potential (from 14 to 49 mV;P < 0.05) and loading capacity increases from 8% to 20% (P < 0.05). Designed NPs had slow drug release profile which was influenced by pH and lecithin concentration. The cumulative percentage of RIF released at pH 7.4 was approximately 93% up to 12 h. In overall, release profile was better than standard drug, even in various pH conditions (pH = 1, 3.4, and 7.4). The Chg/L-RIF NPs may be considered as a promising drug nanocarrier. Conclusions: These NPs release RIF in slow and constant rate, which effectively might eliminate the bacilli and prevent the formation of RIF-resistant bacilli.

Background: The use of imaging techniques is important for prompt diagnosis and treatment of atypical mycobacterial infections; it also reduces the burden of these infections. The purpose of the present study was to determine the association between computed tomography (CT) scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples. Methods: This cross-sectional, observational, comparative study included 50 consecutive patients with pulmonary infection caused by atypical mycobacteria, who were hospitalized in Masih-Daneshvari Hospital of Tehran, Iran during 2012–2017. The association between CT scan findings of pulmonary infection caused by atypical mycobacteria and bacillus count in sputum samples was determined in these patients. Results: The results demonstrated that the presence of nodules smaller than 5 mm in diameter, consolidation, bronchiectasis, and pleural thickening were related to bacillus count in sputum samples (P < 0.05). Conclusion: Some CT scan findings, such as nodule diameter smaller than 5 mm, consolidation, bronchiectasis, and pleural thickening, may be indicators of atypical mycobacterial infection. Increased number of involved lobes with bronchiectasis can promote early diagnosis in patients with higher smear and culture grading.

Nontuberculous mycobacterial (NTM) pulmonary infections can be quite similar to tuberculosis, both clinically and radiologically. However, the treatment protocol is not similar. Mycobacterium simiae is a rare cause of NTM pulmonary infection. Herein, we aimed to evaluate and compare the computed tomography (CT) scan findings of M. simiae infection in lungs. For this reason, thirty-four patients (n=34) with M. simiae lung infection were retrospectively evaluated. Diagnosis was confirmed by American Thoracic Society (ATS) guidelines and CT scans were reviewed in both lung and mediastinal windows. The average age of patients was 63±14.54 years and 52.9% were male. The majority of patients had cough (91.2%) and sputum production (76.5%). Clinically, 41.2% of patients had previous history of TB (14/34), 38.2% had cardiac diseases (13/34), and 35.3% had diabetes mellitus (12/34). The most common CT findings in our study were nodular lesions (100%) and bronchiectasis (85.29%). Regarding the severity, grade I bronchiectasis was the most prevalent. Other prominent findings were tree-in-bud sign (88.2%), consolidation (52.94%), and lobar fibrosis and volume loss (67.6%). There was no significant zonal distribution of findings. In conclusion, nodular lesions and bronchiectasis are the most frequent features in CT scan of M. simiae pulmonary infection.

Objective/Background: Interferon gamma (IFN-γ) plays a key role in protective immune response against Mycobacterial infection. IFN-γ excretes its antimycobacterial effectors mechanisms by activation of macrophages and dendritic cells via interaction with its receptor complex, that is, a ligand-binding subunit [IFN-γ receptor (IFNGR)1] and an accessory subunit (IFNGR2) on the cell surface. It has been shown that individuals with complete or partial IFNGR1 receptor deficiency are highly susceptible to infection by nontuberculous mycobacteria (NTM), Mycobacterium tuberculosis, and some Salmonella species. In the present study, we aimed to study the IFNGR1 T-56C single nucleotide polymorphism (SNP) in pulmonary patients that were infected with rapid grower mycobacterium. Methods: Sputum specimens from suspected nontuberculosis pulmonary patients (n = 95) were digested and decontaminated using 4% NaOH method. Molecular identification of mycobacterium was then performed by hsp65 genes using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Finally, the host genomic DNA from confirmed patients with rapid-grower mycobacterium (n = 20) and control subjects (n = 20) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP. Results: Out of 95 NTM patients, 20 (21.0%) were infected with rapid grower mycobacterium (RGM). The frequency of Mycobacterium chelonae (n = 12) was more than Mycobacterium fortuitum (n = 8), but the differences were not statistically significant. Interestingly, 18 patients (90%) had CC genotypes, whereas the remaining two had TC genotypes. The frequency of CC genotypes in the control group was

Objective/Background: Nontuberculosis mycobacteria (NTM) are a diverse group of microorganisms that cause a variety of diseases in humans including skin, respiratory, and gastrointestinal tract infection. Generally, NTM are classified into two categories: rapid (7 days). In this study, we aimed to investigate NTM frequency and prevalence in environmental samples. Additionally, we tried to identify various subtypes of isolated rapid growing mycobacteria (RGM). Methods: Through a prospective descriptive cross-sectional study, water and soil samples were gathered from four neighboring towns around Tehran, the capital of Iran, at different geographic directions. Every 100m2 of the studied areas gave one sample containing 6g of soil in 3–5 cm depth deposited in 50 mL sterile water as sampling media. After digestion and decontamination, DNA from culture-positive specimens (RGM) were extracted using phenol–chloroform methods. Then the molecular identification of species and subspecies were performed using 16s–23s rRNA and hsp65 gene. Results: In total, 341 RGM were found, out of which 322 (94.4%) were identified and 20 (5.8%) could not be identified. The most frequent RGM was, Mycobacterium fortuitum (72; 22%), Mycobacterium senegalense (58; 17.7%), Mycobacterium parafortuitum (44; 13.4%) and Mycobacterium conceptionense type 1 (24; 7.2%), and Mycobacterium cheloni type 1 (20; 6.0%). As shown in [Table 1], M. fortuitum had more subtypes (8), and the frequency of subtypes 1 (27.7%), 4 (16.6%), and 5 (13.8%) were higher. Among subtypes of M. senegalense, subtype 1 had a higher frequency (70.4%) in comparison to subtype 2 (29.5%). M. cheloni had just one subtype.{Table 1} Conclusion: Our results showed M. fortuitum as the most prominent strain isolated from environmental samples. The frequency was similar in different places, irrespective of climatic variations. Availability of various subtypes of M. fortuitum might indicate a large circulation of this RGM in soil and water of Iranian territory. This high prevalence of M. fortuitum might raise the risk infection, especially in children, immunocompromised patients, diabetics, and cancer cases.

Objective/Background: The susceptibility to tuberculosis (TB) depends upon different factors, and the risk of developing diseases after infection with Mycobacterium tuberculosis ranges from 5% to 10%. This suggests that besides the mycobacterial itself, the host genetic factors may determine the differences in host susceptibility to TB. Among the important risk factors, cytokines and especially tumor necrosis factor alpha (TNF-α) genes, are thought to be responsible for regulating the protective immune responses. The TNF-α gene that encodes the cytokines TNF-α is located within the class III region of the major histocompatibility complex (MHC). The TNF-α gene and its receptors have significant suppressive effects on bacterial growth into macrophages. Tumor necrosis factor receptor 1 (TNFR1) is more responsible when apoptosis is needed but tumor necrosis factor receptor 2 (TNFR2) is involved in cell survival. TNF-α conducts its replicative effects on immune cells via the latter. Up to now, several polymorphisms within the promoter region of the TNF-α gene have been shown to be associated with susceptibility or resistance to TB in different ethnic groups. By contrast, the correlation of TNF-α gene with their receptors such as TNFR2 in susceptibility to TB has not been resolved yet. In this study, we aimed to analyze the single nucleotide polymorphisms (SNPs) in the TNF-α gene at the –238, –308, –857, and –863 positions, and compare the susceptibility to TB with polymorphisms at TNFR2 (T587G). Methods: One hundred fifty-one tuberculosis patients (n = 151) and 83 control subjects (n = 83) were included in this study. Polymorphisms in the TNF promoter region, namely TNF (SNP), –238, –308, –857, and –863 were studied using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). For TNFR2 polymorphisms at 587 positions, the following primers were used to amplify a 242 base pair (bp) product: 5'-TTCTGGAGTTGGCTGCGTGT-3' and ACTCTCCTATCCTGCCTGCT-3'. PCR products of TNFR2 digested with 2U enzymes of NLA III. Results: The current study found a strong correlation between two polymorphisms in different loci of TNF-α gene including 857 C/C (85; 56.2%) and TNF 238 A/A 127 (84.1%). However, there were no associations between polymorphisms of the TNF-α gene and its receptor, that is, TNFR2. Conclusion: Concerning our current study, screening assessments for TNF-α-857 and A238GSNPs in Iran would be important in order to make future decisions for preventive treatments before getting the disease among individuals who are at high risk considering their genotyping.

During recent years, the implication of nanoparticles (NPs) as drug delivery systems has gained much scientific attention. As drugs do not deliver themselves, a nanoparticle can act by optimizing drug delivery in the right place, at the right time and at the right dosage. In previous years, this research successfully developed and evaluated the ChPL-NPs nanoparticles (chitosan protein–lipid) [US patent pending 20140370500]. In the present investigation, rifampicin (RIF) ChPL-NPs nanoparticles were designed and developed. Consequently, the in vitro release of RIF ChPL-NPs nanoparticles was investigated. Material and Methods: Briefly, chitosan powder (90 KD and 90% degree of deacetylation) was dissolved (1% acetic-acid) and mixed with gelatin (3%). Then, the lipid and rifampin in ether was precipitated by rotary vacuum evaporator. Under high speed homogenizer (12,000rpm), both solutions (chitosan–gelatin & rifampin–lipid) were mixed [US patent pending 20140370500]. The obtained RIF ChPL-NPs were put into a dialysis bag with cut-off 14 KD in phosphate buffer solution (pH=7.4). The release of RIF was obtained by reverse phase HPLC using C18 (250 × 4.6 mm, 5 μm) column. The mobile phase consisted of 50:50 v/v acetonitrile and 10 mm potassium dihydrogen phosphate (pH=3.2) and flow rate 1 ml/min. The column temp was maintained at 25 °C with UV detection at 335nm. Results and conclusions: The average size of RIF ChPL-NPs was about 50–250nm. The release of RIF from the dialysis bag started after 30 min which was 2400ng/ml; after 16 h the release of RIF was 15,000ng/ml; and at 40 h the concentration reached to 19,600ng/ml. Therefore, these results showed a slow release of RIF from ChPL-NPs. Basically, the intensity of the surface charges in nanoparticle is important as it determines their interaction with bioactive compound. In RIF ChPL-NPs, lipid had negative charges, whereas chitosan and gelatin had positive charges. The electrostatic interaction between oppositely charged ions would ultimately cause an effective system drug delivery. RIF ChPL-NPs is not only suitable for intravenous administration, but it can be used as an inhalation aerosol, because this nanoparticle has a capacity to adhere to mucosal surfaces and transiently open the tight junction.