Production and Evaluation of Ag85B:HspX:hFcγ1 Immunogenicity as an Fc Fusion Recombinant Multi-Stage Vaccine Candidate Against Mycobacterium tuberculosis.

An urgent need is to introduce an effective vaccine against Mycobacterium tuberculosis (M.tb) infection. In the present study, a multi-stage M.tb immunodominant Fcγ1 fusion protein (Ag85B:HspX:hFcγ1) was designed and produced, and the immunogenicity of purified protein was evaluated. This recombinant fusion protein was produced in the Pichia pastoris expression system. The HiTrap-rPA column affinity chromatography purified and confirmed the fusion protein using ELISA and Western blotting methods. The co-localisation assay was used to confirm its proper folding and function. IFN-γ, IL-12, IL-4, and TGF-ß expression in C57BL/6 mice then evaluated the immunogenicity of the construct in the presence and absence of BCG. After expression optimisation, medium-scale production and the Western blotting test confirmed suitable production of Ag85B:HspX:hFcγ1. The co-localisation results on antigen-presenting cells (APCs) showed that Ag85B:HspX:hFcγ1 properly folded and bound to hFcγRI. This strong co-localisation with its receptor can confirm inducing proper Th1 responses. The in vivo immunisation assay showed no difference in the expression of IL-4 but a substantial increase in the expression of IFN-γ and IL-12 (P ≤ 0.02) and a moderate increase in TGF-ß (P = 0.05). In vivo immunisation assay revealed that Th1-inducing pathways have been stimulated, as IFN-γ and IL-12 strongly, and TGF-ß expression moderately increased in Ag85B:HspX:hFcγ1 group and Ag85B:HspX:hFcγ1+BCG. Furthermore, the production of IFN-γ from splenocytes in the Ag85B:HspX:hFcγ1 group was enormously higher than in other treatments. Therefore, this Fc fusion protein can make a selective multi-stage delivery system for inducing appropriate Th1 responses and is used as a subunit vaccine alone or in combination with others.

Probiotics as a Promising Therapy in Improvement of Symptoms in Children With ADHD: A Systematic Review.

BACKGROUND: ADHD is widely recognized as the most prevalent neurodevelopmental disorder in children. Recently, the potential role of gut microbiota as an etiological factor in ADHD has gained attention. This systematic review aims to investigate the potential impact of probiotic supplements on alleviating ADHD symptoms and influencing behavior. METHODS: PubMed, Web of Science, Cochrane Library, and SCOPUS were searched from inception to May 2023. Only randomized controlled trials that have suitable data of the effects of probiotics/synbiotics on children with ADHD were enrolled. The risk of bias of the included studies was assessed by Cochrane Collaboration risk of bias tool. RESULTS: Five related randomized controlled trial were evaluated in the current review. Types of interventions ranged from single/multi strain probiotics to synbiotic. The duration of intervention in all of the studies were 2 to 3 months. The assessed outcomes were very diverse and different tools were used to report the symptoms in children. Among those which used Conners' Parent Rating Scale, a decrease in the total score occurred in the probiotic group, compared to the placebo group. An improvement in both intervention and control groups was seen in one study which used ADHD-Rating Scale. CONCLUSION: In summary, the combined findings from the reviewed studies suggest that probiotic supplements might potentially serve as a complementary intervention for ADHD. However, given the small number of studies, limited sample sizes, and the diversity of probiotic strains, further research is needed to clarify the effects of probiotics in children with ADHD. The observed tolerability of probiotics is noteworthy as none of the studies report adverse effects.

Statins, allies against antibiotic resistance?

Due to the ever-increasing rate of antibacterial resistance, the search for effective antibacterial agents has become imperative. Researchers have investigated the potential antimicrobial properties of various classes of nonantibiotic drugs. Statins are a group of antihyperlipidemic drugs with several cholesterol-independent effects, including anti-inflammatory, immune-modulating, antioxidant, and antibacterial effects. In vitro and in vivo studies have demonstrated the antibacterial properties of statins against various gram-positive and gram-negative bacteria. Simvastatin and atorvastatin are the most potent members of the family. Their antibacterial effect can be attributed to several direct and indirect mechanisms. Bacterial invasion, growth, and virulence are affected by statins. However, since in vitro minimum inhibitory concentrations (MICs) are significantly higher than serum concentrations at the lipid-lowering dosage, indirect mechanisms have been suggested to explain the positive clinical results, including reducing inflammation and improving immune response capacity. Further, statins have shown promising results when combined with antibiotics and other antibacterial agents, such as triazenes and silver nanoparticles. Despite this, the controversial aspects of statins have cast doubt on their efficacy as a possible solution for antibacterial resistance, and further research is required. Consequently, this review will examine in detail the current clinical and in vitro findings and controversies regarding statins' antibacterial properties and their relevance to antibacterial resistance.

Anticancer activity of Pseudomonas aeruginosa derived peptide with iRGD in colon cancer therapy.

Objectives: Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer. Materials and Methods: Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR. Results: These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis. Conclusion: It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU.

Rate of occult hepatitis B virus infection among individuals with tuberculosis in northeastern Iran: A molecular epidemiological study.

One third of the world population has a history of exposure to the hepatitis B virus (HBV), and two billion people are infected with latent tuberculosis (TB). Occult hepatitis B infection (OBI) is defined as the presence of replicative-competent HBV DNA in the liver with detectable or undetectable HBV DNA in the serum of individuals testing negative for the HBV surface antigen (HBsAg). Screening with HBV DNA could identify OBI and significantly reduce carriers and complications of chronic hepatitis B (CHB). This study aims to assess HBV serological markers and OBI molecular diagnosis among people with TB in Mashhad, northeastern Iran. We have performed HBV serological markers (HBsAg, HBc antibodies (Ab) and HBs Ab) in 175 participants. Fourteen HBsAg+ sera were excluded for further analysis. The presence of HBV DNA (C, S, and X gene regions) was assessed by the qualitative real-time PCR (qPCR) method. Frequencies of HBsAg, HBc, and HBs Ab were 8% (14/175), 36.6% (64/175), and 49.1% (86/175), respectively. Among these 42.9% (69/161) were negative for all HBV serological markers. The S, C, and X gene regions were positive in 10.3% (16/156), 15.4% (24/156), and 22.4% (35/156) of participants, respectively. The total OBI frequency was estimated at 33.3% (52/156) when based on detecting one HBV genomic region. Twenty-two and 30 participants had a seronegative and seropositive OBI, respectively. Thorough screening of high-risk groups with reliable and sensitive molecular methods could lead to OBI identification and decrease CHB long-term complications. Mass immunization remains critical in preventing, reducing, and potentially eliminating HBV complications.

Design of a rapid electrochemical biosensor based on MXene/Pt/C nanocomposite and DNA/RNA hybridization for the detection of COVID-19.

Since the rapid spread of the SARS-CoV-2 (2019), the need for early diagnostic techniques to control this pandemic has been highlighted. Diagnostic methods based on virus replication, such as RT-PCR, are exceedingly time-consuming and expensive. As a result, a rapid and accurate electrochemical test which is both available and cost-effective was designed in this study. MXene nanosheets (Ti3C2Tx) and carbon platinum (Pt/C) were employed to amplify the signal of this biosensor upon hybridization reaction of the DNA probe and the virus's specific oligonucleotide target in the RdRp gene region. By the differential pulse voltammetry (DPV) technique, the calibration curve was obtained for the target with varying concentrations ranging from 1 aM to 100 nM. Due to the increase in the concentration of the oligonucleotide target, the signal of DPV increased with a positive slope and a correlation coefficient of 0.9977. Therefore, at least a limit of detection (LOD) was obtained 0.4 aM. Furthermore, the specificity and sensitivity of the sensors were evaluated with 192 clinical samples with positive and negative RT-PCR tests, which revealed 100% accuracy and sensitivity, 97.87% specificity and limit of quantification (LOQ) of 60 copies/mL. Besides, various matrices such as saliva, nasopharyngeal swabs, and serum were assessed for detecting SARS-CoV-2 infection by the developed biosensor, indicating that this biosensor has the potential to be used for rapid Covid-19 test detection.

Role of host immunity and HBx among inactive chronic hepatitis B patients in a highly endemic region.

The hepatitis B virus (HBV) infection has a wide range, from fulminant hepatitis to inactive chronic hepatitis B (ICB) infection. The present study evaluated critical factors in the outcomes of HBV infection in a highly endemic region of Iran (approximately 12% HBV positive). The expression of seven genes involved in host immunity (Foxp3, T-bet, ROR-γt, AKT, CREB, IL-28/or IFN-λ2, and IL-28R) and HBx for viral activities were evaluated using real-time PCR, TaqMan method. A total of 58 subjects were randomly chosen, including 28 ICB and 30 healthy controls (HCs) from the Esfandiar district, South Khorasan province, Iran. The expression index of Foxp3 and ROR-γt was moderately up-regulated in ICBs but did not statistically significant. T-bet expression in ICB patients was significantly higher than in HCs (p = 0.004). Furthermore, evaluating two signalling pathways in Th activation and cell survival showed that the CREB pathway was significantly up-regulated in ICB patients compared to HCs (p = 0.006), but the AKT did not differ. In innate immune responses, the IL-28/or IFN-λ2 expression in ICB patients was significantly higher than in the HCs (p = 0.02). Surprisingly, only one ICB patient disclosed HBx expression, which shows deficient virus activity in these patients. The ICB condition seems to result from host immune pressure on HBV activities, up-regulation of T-bet and IFN-λ. The high expression of CREB may prevent Kupffer's pro-inflammatory reactions in the liver. Whereas the absence of HBx expression in ICB patients and, consequently, the inactivity of HBV may also confirm such immune pressure.

Role of lactobacillus strains in the management of colorectal cancer: An overview of recent advances.

Colorectal cancer (CRC) remains one of the most frequently occurring cancers worldwide. Current standard therapeutic drugs have been associated with serious side effects that can be life-threatening for some patients. Extensive efforts have been undertaken to find alternative therapies. Probiotic bacteria are among new therapeutic options under evaluation. Lactobacilli strains are among the most used probiotics in CRC. Recent studies have shown that consumption of lactobacillus strains, alone or in combination with standard chemotherapy drugs for CRC have exerted beneficial effects on tumor development and growth via several mechanisms, including induction of apoptosis, immunomodulation of inflammatory cytokines, and changing profile of gut microbial community. They affect the signaling pathways involved in cell migration and invasion leading to hampering of tumor metastatic behavior. This review summarizes recent experimental findings regarding antitumor function of the most used lactobacillus species in CRC, providing more supporting data for introducing probiotics as new encouraging therapeutic strategy in cancer prevention and treatment.

Bacterial Peptides and Bacteriocins as a Promising Therapy for Solid Tumor.

The conventional treatment is faced with limitations in treating solid tumors due to their specific pathophysiology. Several novel therapeutics have been introduced in recent decades to treat solid tumors. Among these new methods, tumor therapy using bacterial products like bacteriocins and peptides has been of great interest due to their unique characteristics and advantages of them in comparison to the conventional treatment, including that they can precisely target tumor cells, selective toxicity for tumor cells, low side effect on normal cells, toxicity activity for MDR cancer cells, used as the target delivery vehicles and enhancing drug delivery. Moreover, their small size and low molecular weight have made them easy to synthesize and modify. Furthermore, in recent years, genetic engineering has expanded the therapeutic ability of peptides to treat solid tumors, which results in overcoming the peptide drawbacks. The present review mainly focuses on the new advances in applying bacterial peptides and bacteriocins in treating human solid tumors.

TAX and HBZ: hFc Ɣ 1 proteins as targets for passive immunotherapy.

Objectives: Human T leukemia virus type one (HTLV-1) causes two life-threatening diseases in around five percent of infected subjects, a T cell malignancy and a neurodegenerative disease. TAX and HBZ are the main virulence agents implicated in the manifestation of HTLV-1-associated diseases. Therefore, this study aims to produce these HTLV-1 factors as recombinant Fc fusion proteins to study the structures, their immunogenic properties as vaccines, and their capability to produce specific neutralization antibodies. Materials and Methods: TAX and HBZ sequences were chosen from the NCBI-nucleotide database, then designed as human Fc chimers and cloned into Pichia pastoris. Produced proteins were purified by HiTrap affinity chromatography and subcutaneously injected into rabbits. Rabbit Abs were purified by batch chromatography, and their neutralization activities for the HTLV-1-infected MT-2 cell line were assessed. Furthermore, the protective abilities of recombinant proteins were evaluated in Tax or HBZ immunized rabbits by MT-2 cell line inoculation and measurement of HTLV-1-proviral load. Results: Specific Abs against Tax and HBZ can eliminate 2 million MT-2 cells in 1/1000 dilution in vitro. In challenging assays, the immunization of the animals using Tax or HBZ had no protective activity as HTLV-1 PVL was still positive. Conclusion: The result suggests that recombinant TAX and HBZ: hFcγ1 proteins can produce a proper humoral immune response. Therefore, they could be considered a passive immunotherapy source for HTLV-1-associated diseases, while total TAX and HBZ proteins are unsuitable as HTLV-1 vaccine candidates.

Detection of Isoniazid and Rifampin Resistance in Mycobacterium tuberculosis Clinical Isolates from Sputum Samples by High-Resolution Melting Analysis.

The effective management of multidrug-resistant tuberculosis (MDR-TB) and the need for rapid and accurate screening of rifampin (RIF) and isoniazid (INH)-resistant Mycobacterium tuberculosis (Mtb) isolates are the most fundamental and difficult challenges facing the global TB control. The present study aimed to compare the diagnostic accuracy of high-resolution melting-curve analysis (HRMA) in comparison to multiplex allele-specific PCR (MAS-PCR) and xpert MTB/RIF as well as the conventional drug-susceptibility test (DST) and gene sequencing for the detection of INH and RIF resistance in the Mtb isolates. In the present study, a total of 431 Mtb isolates including 11 MDR (%2.55), 7 INH resistance (%1.62), two RIF resistance (%0.46), and 411 sensitive isolates were phenotypically confirmed. HRMA assay identified katG gene mutations and the mabA-inhA promoter region in 15 of 18 INH-resistant samples and rpoB gene mutations were successfully evaluated in 11 out of 13 RIF-resistant samples. The sensitivity and specificity of the HRMA method were 83.3% and 98.8% for INH and 84.6% and 99% for RIF, respectively. The most common mutation in RIF-resistance-determining region (RRDR) occurred at codon 531 (TCG → TTG)(84.6%) and then at codon 513 (CAA → GTA)(7.6%) and 526 (CAC → TAC) (7.6%), which resulted in the amino-acid changes. Also, 88.8% of INH-resistant samples had mutations in the katG gene and the mabA-inhA promoter region, of which the highest mutation occurred at codon 315 (AGC → ACC) of the katG gene. In conclusion, all these results indicated that the sensitivity and specificity of the HRM method were increased when the katG gene and the mabA-inhA promoter region were used as a target.

A century of attempts to develop an effective tuberculosis vaccine: Why they failed?

Tuberculosis (TB) remains a major global health problem despite widespread use of the Bacillus BCG vaccine. This situation is worsened by co-infection with HIV, and the development of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains. Thus, novel vaccine candidates and improved vaccination strategies are urgently needed in order to reduce the incidence of TB and even to eradicate TB by 2050. Over the last few decades, 23 novel TB vaccines have entered into clinical trials, more than 13 new vaccines have reached various stages of preclinical development, and more than 50 potential candidates are in the discovery stage as next-generation vaccines. Nevertheless, why has a century of attempts to introduce an effective TB vaccine failed? Who should be blamed -scientists, human response, or Mtb strategies? Literature review reveals that the elimination of latent or active Mtb infections in a given population seems to be an epigenetic process. With a better understanding of the connections between bacterial infections and gene expression conditions in epigenetic events, opportunities arise in designing protective vaccines or therapeutic agents, particularly as epigenetic processes can be reversed. Therefore, this review provides a brief overview of different approaches towards novel vaccination strategies and the mechanisms underlying these approaches.

Sensitive and specific clinically diagnosis of SARS-CoV-2 employing a novel biosensor based on boron nitride quantum dots/flower-like gold nanostructures signal amplification.

The sudden increase of the COVID-19 outbreak and its continued growth with mutations in various forms has created a global health crisis as well as devastating social and economic effects over the past two years. In this study, a screen-printed carbon electrode reinforced with boron nitride quantum dots/flower-like gold nanostructures (BNQDs/FGNs/SPCE) and functionalized by highly specific antisense DNA oligonucleotide presents an alternative and promising solution for targeting SARS-CoV-2 RNA without nucleic acid amplification. The platform was tested on 120 SARS-CoV-2 RNA isolated from real clinical samples (60 positive and 60 negative confirmed by conventional RT-PCR method). Based on obtained quantitative results and statistical analysis (box-diagram, cutoff value, receiver operating characteristic curve, and t-test), the biosensor revealed a significant difference between the two positive and negative groups with 100% sensitivity and 100% specificity. To evaluate the quantitation capacity and detection limit of the biosensor for clinical trials, the detection performance of the biosensor for continuously diluted RNA isolated from SARS-CoV-2-confirmed patients was compared to those obtained by RT-PCR, demonstrating that the detection limit of the biosensor is lower than or comparable to that of RT-PCR. The ssDNA/BNQDs/FGNs/SPCE showed negligible cross-reactivity with RNA fragments isolated from Influenza A (IAV) clinical samples and also remained stable for up to 14 days. In conclusion, the fabricated biosensor may serve as a promising tool for point-of-care applications.

Green synthesis of selenium nanoparticles using Rosmarinus officinalis and investigated their antimicrobial activity.

The interest of many has been attracted by plant-mediated synthesizing procedures for nanoparticles since they provide certain qualities including being cost-effective, quick, and compatible with the environment. In this regard, this work introduces the production of selenium-nanoparticles (Se-NPs) in a biological manner utilizing aqueous extracts of Rosmarinus officinalis (R. officinalis). Production of Se-NPs was confirmed using UV-visible (UV-Vis) spectrophotometry. Also, dynamic light scattering (DLS) analysis was used for determination particle size distribution, while we distinguished the identification of crystalline construction of nanoparticles through the means of X-ray diffraction (XRD) pattern, DLS, and transmission electron microscopy (TEM) examination indicated that Se-NPs are often spherical with a size about 20 to 40 nm. The minimum inhibitory concentration (MIC) of the synthesized Se-NPs by R. officinalis extract against Mycobacterium tuberculosis (M. tuberculosis), Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) was 256, 16, 32, 128, and 64 µg/mL, respectively. The synthesized Se-NPs had no significant effect on Mycobacterium simiae (M. simiae) and had exhibited a strong antimicrobial functionality towards the gram-positive and gram-negative bacteria and can stand as a potent antibacterial agent.

Emerging roles of CD133 in the treatment of gastric cancer, a novel stem cell biomarker and beyond.

Gastric cancer (GC) is an aggressive disease with one of the highest mortality rates in the world. In the early stage, most patients are asymptomatic and early diagnosis is difficult. Recently, cancer stem cells (CSCs) have been highlighted as crucial emerging factors in the initiation or invasiveness of solid tumors. CD133, a CSC marker, is highly expressed in various tumors including gastric cancer. CD133-positive cells showed elevated malignant biological behaviors and CD133 upregulation is related to chemoresistance, cancer relapse, and poor prognosis. CD133 also plays an important role in the progression of tumors and metastasis. This review summarizes the current knowledge of the role of CD133 expression in GC and aims to contribute at identifying promising new strategies for treatment and management of gastric cancer.

A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.

The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.

The Chance of COVID-19 Infection after Vaccination.

The outbreak of COVID-19 that was first reported in Wuhan, China, has constituted a new emerging epidemic that has spread around the world. There are some reports illustrating the patients getting re-infected after recovering from COVID-19. Here, we provide an overview of the biphasic cycle of COVID-19, genetic diversity, immune response, and a chance of reinfection after recovering from COVID-19. The new generation of COVID-19 is a highly contagious and pathogenic infection that can lead to acute respiratory distress syndrome. Whilst most patients suffer from a mild form of the disease, there is a rising concern that patients who recover from COVID-19 may be at risk of reinfection. The proportion of the infected population is increasing worldwide; meanwhile, the rate and concern of reinfection by the recovered population are still high. Moreover, there is little evidence on the chance of COVID-19 infection even after vaccination, which is around one percent or less. Although the hypothesis of zero reinfections after vaccination has not been clinically proven, further studies should be performed on the recovered class in clusters to study the progression of the exposure with the re-exposed subpopulations to estimate the possibilities of reinfection and, thereby, advocate the use of these antibodies for vaccine creation.

Designing and development of epitope-based vaccines against Helicobacter pylori.

Helicobacter pylori infection is the principal cause of serious diseases (e.g. gastric cancer and peptic ulcers). Antibiotic therapy is an inadequate strategy in H. pylori eradication because of which vaccination is an inevitable approach. Despite the presence of countless vaccine candidates, current vaccines in clinical trials have performed with poor efficacy which makes vaccination extremely challenging. Remarkable advancements in immunology and pathogenic biology have provided an appropriate opportunity to develop various epitope-based vaccines. The fusion of proper antigens involved in different aspects of H. pylori colonization and pathogenesis as well as peptide linkers and built-in adjuvants results in producing epitope-based vaccines with excellent therapeutic efficacy and negligible adverse effects. Difficulties of the in vitro culture of H. pylori, high genetic variation, and unfavourable immune responses against feeble epitopes in the complete antigen are major drawbacks of current vaccine strategies that epitope-based vaccines may overcome. Besides decreasing the biohazard risk, designing precise formulations, saving time and cost, and induction of maximum immunity with minimum adverse effects are the advantages of epitope-based vaccines. The present article is a comprehensive review of strategies for designing and developing epitope-based vaccines to provide insights into the innovative vaccination against H. pylori.

Anti-mycobacterial Activity of 22 Iranian Endemic or Rare Plant Extracts Against Multi-drug and Extensively Drug-resistant Mycobacterium tuberculosis.

BACKGROUND: Due to side-effects and low efficacy of common drugs on new resistant strains of Mycobacterium tuberculosis (Mtb), investigation on novel drugs and natural compounds from rich sources of endemic plants is required. Thus, in the present study, the anti-mycobacterial effects of 22 Iranian endemic or rare plant extracts on multi-drug resistance (MDR) and extensively-drug resistance (XDR) Mtb isolates were evaluated. METHODS: Twenty-two Iranian endemic and rare plant species from 9 families were collected and extracted by methanol. Their inhibitory-effects were then evaluated against Mtb H37Rv strain, seven clinical MDR-TB, and two XDR-TB isolates using the resazurin microtiter assay (REMA) method. The best of them were then fractionalized by five different polar solvents (Petroleum- Ether, Dichloromethane, Ethyl-Acetate, n-butanol, and water). To find anti-mycobacterial fractions, the inhibitory effect of isolated fractions was tested on Mtb H37Rv. RESULTS: Out of the 22 plants, 14 plant extracts demonstrated anti-mycobacterial activity with minimum inhibitory concentration (MIC) ranging from 4 to 30µg/mL against Mtb H37Rv. Eight plant extracts also exhibited anti-mycobacterial activity against MDR and XDR clinical strains of Mtb by MICs, i.e., 15-60µg/ml. Crinitaria grimmii and Linum album were the best antimycobacterial plants. Among fractions of Crinitaria grimmii, dichloromethane and n-butanol, and for Linum album, dichloromethane and Ethyl-Acetate fractions displayed more anti-mycobacterial effect as compared to crude extract on Mtb. CONCLUSION: The present study confirms the potential role of some plants to treat respiratory diseases as our results have demonstrated that these plants exhibit anti-mycobacterial activity in the acceptable range against Mtb. Thus, these plants could be good sources and alternatives of plant metabolites for anti-TB-drug development.

Previous pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis.

PURPOSE: The possible association between history of pulmonary tuberculosis (TB) and lung cancer (LC) has attracted researchers' attention for several decades. This systematic review and meta-analysis aim to assess the association between previous pulmonary TB infection and LC risk. METHODS: A Systematic and comprehensive search was performed in the following databases: PubMed, Embase, clinical key, Web of Science and Google Scholar, in articles and abstracts published from 1987 to 2021. Thirty-two articles (involving 50,290 cases and 846,666 controls) met the inconclusive criteria. The Comprehensive Meta-Analysis version 2.2 software was used for this meta-analysis. RESULTS: The result of this meta-analysis demonstrates that pre-existing active pulmonary TB increases the risk of LC (RR = 2.170, 95% confidence interval [CI] 1.833-2.569, p < .001, I2 = 91.234%). The results showed that the risk of the history of active pulmonary TB infection in adenocarcinoma was 2.605 (95% CI 1.706-3.979, p < .001, I2 = 55.583%), in small-cell carcinoma was 2.118 (95% CI 1.544-2.905, p < .001, I2 = 0.0%), in squamous-cell carcinoma, was 3.570 (95% CI 2.661 - 4.791, p < .001, I2 = 42.695%) and 2.746 (95% CI 2.300-3.279, p < .001, I2 = 41.686%) for other histological types of LCs. According to these results, a history of active pulmonary TB increases the risk of LC. CONCLUSIONS: This study emphasizes the importance of LC screening in pulmonary TB patients even after the infection is treated. With the increased chances of LC in a patient who had a history of active pulmonary TB, there could be a need for a further follow-up period after pulmonary TB recovery.