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.

The bacterial instrument as a promising therapy for colon cancer.

OBJECTIVE: Colon cancer is a great health concern worldwide, as it is the second leading cause of cancer-related death. Conventional treatment of cancer such as surgery, radiotherapy, and chemotherapy are faced with limitations and side effects. Therefore, strategies for the treatment of cancer need to be modified or new strategies replacing the old one. AIMS: The aim of this study is to review the role of bacteria or their products (such as peptides, bacteriocins, and toxins) as a therapeutic agent for colon cancer. RESULTS AND CONCLUSION: Recently, the therapeutic role of bacteria and their products in colon cancer treatment holds promise as emerging novel anti-cancer agents. Unlike the conventional treatments, targeted therapy based on the use of bacteria that are able to directly target tumor cells without affecting normal cells is evolving as an alternative strategy. Moreover, several bacterial species were used in live, attenuated or genetically modified that are able to multiply selectively in tumors and inhibiting their growth.

Bacteriotherapy in Breast Cancer.

Breast cancer is the second most common cause of cancer-related mortality among women around the world. Conventional treatments in the fight against breast cancer, such as chemotherapy, are being challenged regarding their effectiveness. Thus, strategies for the treatment of breast cancer need to be continuously refined to achieve a better patient outcome. We know that a number of bacteria are pathogenic and some are even associated with tumor development, however, recent studies have demonstrated interesting results suggesting some bacteria may have potential for cancer therapy. Therefore, the therapeutic role of bacteria has aroused attention in medical and pharmaceutical studies. Furthermore, genetic engineering has been used in bacterial therapy and may led to greater efficacy with few side effects. Some genetically modified non-pathogenic bacterial species are more successful due to their selectivity for cancer cells but with low toxicity for normal cells. Some live, attenuated, or genetically modified bacterias are capable to multiply in tumors and inhibit their growth. This article aims to review the role of bacteria and their products including bacterial peptides, bacteriocins, and toxins for the treatment of breast cancer.

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.

Effect of the Previous History of the SARS-CoV-2 Infections on Antibody Levels among Sputnik V Vaccinated Healthcare Workers.

Background: Measuring the level of antibodies produced post-vaccination in response to the SARS-CoV-2 spike protein is considered a strategy for estimating the effectiveness of the COVID-19 vaccines. Objective: To examine the antibody levels among the healthcare workers in different hospitals in Mashhad, Iran after receiving the second dose of Sputnik V. Methods: In this study, we enrolled 230 healthcare workers for evaluating the Gam-COVID-Vac or Sputnik V after the second administration in different hospitals in Mashhad. Antibody levels of spike protein were quantitatively evaluated in a sample of 230 negative RT-PCR tests for the COVID-19 individuals. The analysis has been done based on an immunological assay using enzyme-linked immunosorbent assay (ELISA). The infection history of the subjects and their families was examined through their medical records. Results: Our results demonstrated a significant association between a higher titer of IgG and a previous history of the COVID-19 infection (P<0.001). Moreover, the chance of detecting antibodies titer more than 50 AU/ml was 16.99 in these people which was significantly higher than in people without a history of infection pre-vaccination [%95CI: (7.38,39.12), P<0.001]. Conclusion: This result demonstrates that the efficacy of antibody production is related to the previous history of the SARS-CoV-2 infections. Ongoing monitoring of the level of antibody among vaccinated populations will help evaluating the effect of vaccines on humoral immunity status.

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.

Evaluation of the therapeutic effect of melittin peptide on the ulcerative colitis mouse model.

BACKGROUND: Ulcerative colitis (UC) is considered one of the most prevalent inflammatory bowel diseases (IBDs). However, due to the lack of satisfying efficacy of conventional therapies and their side effects, there is still a need for more efficient therapeutic agents. Melittin is a small peptide derived from bee venom, which shows potent anti-inflammatory activity. The present investigation aimed to assess the anti-inflammatory effect of melittin peptide alone and in co-therapy with sulfasalazine as a standard therapy on dextran sulfate sodium (DSS)-induced colitis models. MATERIAL AND METHODS: We used DSS to induce UC in C57BL/6 male mice. We investigated the effect of melittin peptide alone and in combination with sulfasalazine on improving the clinical symptoms among DSS-induced colitis models. Finally, we employed histological investigation to show the therapeutic effect of melittin on attenuating the pathological damage of colon tissue caused due to DSS-induced inflammation in colitis models. RESULTS: Our findings demonstrated that melittin peptide alone and in combination with sulfasalazine dramatically cured the clinical UC. Moreover, we observed that this peptide almost eliminated the histological damage of colon tissue in colitis, while significantly reducing the inflammation in colon tissue. Meanwhile, our results demonstrated that this peptide had an antioxidant effect through the disruption of the oxidant/antioxidant balance. CONCLUSION: All these findings suggest that melittin peptide has an anti-inflammatory effect and can probably be considered a novel therapeutic agent for UC. Furthermore, our results demonstrated that this peptide can enhance the therapeutic effects of conventional therapy while attenuating the adverse effects of conventional agents.

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.

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.

COVID-19 vaccine: where are we now and where should we go?

INTRODUCTION: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has currently caused the pandemic with a high progressive speed and has been considered as the global public health crisis in 2020. This new member of the coronavirus family has created a potentially fatal disease, called coronavirus disease-2019 (COVID-19). Despite the continuous efforts of researchers to find effective vaccines and drugs for COVID-19, there is still no success in this matter. AREAS COVERED: Here, the literature regarding the COVID-19 vaccine candidates currently in the clinical trials, as well as main candidates in pre-clinical stages for development and research, were reviewed. These candidates have been developed under five different major platforms, including live-attenuated vaccine, mRNA-based vaccine, DNA vaccines, inactivated virus, and viral-vector-based vaccine. EXPERT OPINION: There are several limitations in the field of the rapid vaccine development against SARS-CoV-2, and other members of the coronavirus family such as SARS-CoV and MERS-CoV. The key challenges of designing an effective vaccine within a short time include finding the virulence ability of an emerging virus and potential antigen, choosing suitable experimental models and efficient route of administration, the immune-response study, designing the clinical trials, and determining the safety, as well as efficacy.

An effective drug against COVID-19: reality or dream?

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is well known as a novel member of the coronavirus family which caused a sudden outbreak of Coronavirus disease-2019 (COVID-19) in China that quickly developed into a global pandemic. No effective approaches are found as yet for the therapy and epidemiological control of this new virus. We searched the literature in PubMed, Scopus, Web of Knowledge, Google Scholar, and MeSH, for articles and abstracts describing SARS-CoV-2, COVID-19, pneumonia, clinical trials, drug, treatment, and medicine.Areas covered: The present study aimed to comprehensively overview the current literature on effective anti-SARS-CoV-2 drugs.Expert opinion: Since the beginning of this pandemic disease, many studies have been conducted to find effective drugs to prevent COVID-19, because there are no specific drugs for the treatment of this disease. Most of these drugs with the antiviral potential effect toward COVID-19 are already used as the treatment of other infectious diseases. Some drugs that show the promising therapeutic potential in the initial clinical studies include remdesivir as an inhibitor of RNA-dependent RNA polymerase and favipiravir as an inhibitor of virus replication. Currently, remdesivir received the FDA authorizes to use as an experimental drug for emergency use in COVID-19 patients.

Coronaviruses construct an interconnection way with ERAD and autophagy.

Coronaviruses quickly became a pandemic or epidemic, affecting large numbers of humans, due to their structural features and also because of their impacts on intracellular communications. The knowledge of the intracellular mechanism of virus distribution could help understand the coronavirus's proper effects on different pathways that lead to the infections. They protect themselves from recognition and damage the infected cell by using an enclosed membrane through hijacking the autophagy and endoplasmic reticulum-associated protein degradation pathways. The present study is a comprehensive review of the coronavirus strategy in upregulating the communication network of autophagy and endoplasmic reticulum-associated protein degradation.

Therapeutic effect of an anti-tuberculosis agent, isoniazid, and its nano-isoform in ulcerative colitis.

BACKGROUND: Isoniazid (INH) is well known as a first-line anti-tuberculosis, while some studies demonstrate that it has anti-inflammatory activity via a different mechanism such as inhibitionthe production of IL-1, ROS, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1. The aim of this study, investigate the anti-inflammatory effect of INH and INH combined with Sulfasalazine-loaded nanoparticles (NPs) in the ulcerative colitis mouse model. METHODS: To investigate the anti-inflammatory effect of INH and NPs in the ulcerative colitis mice model, we evaluated the effect of INH clinical symptoms and colonic mucosal histology in colitis. RESULT: The present study demonstrates that combination therapy of INH with sulfasalazine as well as NPs reduces the symptom of ulcerative colitis and improved disease activity index include body lose weight, diarrhea, rectal bleeding, colonic length, spleen weight, and colon histopathological score in DSS-induced colitis mice model. CONCLUSION: Our results suggest that the nanoforms of INH with sulfasalazine enhances the therapeutic effect of the drugs in the treatment of ulcerative colitis.

Cerium oxide nanoparticles acts as a novel therapeutic agent for ulcerative colitis through anti-oxidative mechanism.

BACKGROUND: Cerium (IV) oxide (CeO2) exhibit anti-inflammatory activity via scavenge free radicals and decreasing the oxygen species (ROS) production. Here we aimed to exhibit the therapeutic effect of this nanoparticle in experimental colitis models. METHODS: Cerium oxide nanoparticles (CeONPs) were synthesized via using UiO-66 as a precursor. We used dextran sodium sulfate (DSS) to induce colitis in experimental models to investigate the anti-inflammatory effect of CeONPs. Colitis models are divided into four groups to receive the treatment, including control, colitis, cerium oxide, and sulfasalazine. We evaluated the therapeutic effects of CeONPs for the increased colitis clinical symptoms and attenuated the histological damage to colon tissue in colitis. RESULT: This nanoparticle was significantly able to reduce the clinical symptoms of colitis. Moreover, CeONPs can enhance the disease activity index such as body lose weight, diarrhea, rectal bleeding, colon length, and spleen weight. Moreover, CeONPs showed a significant reduction in the histological characteristics of the colitis models. CONCLUSION: These results suggest that CeONPs can be considered as promising therapeutic agents in treating the ulcerative colitis.

Anticancer activity of Helicobacter pylori ribosomal protein (HPRP) with iRGD in treatment of colon cancer.

PURPOSE: As the conventional therapeutic approaches were not completely successful in the treatment of colon cancer, there is still a need for finding the most efficient therapeutic agents. Here we investigated the anticancer activity of HPRP-A1 that was derived from the N-terminal region of Helicobacter pylori ribosomal protein L1 (RpL1) alone or in combination with tumor-homing peptide iRGD and 5-Fluorouracil (5FU) on colon cancer cell lines (CT26 and HT29) and isograft models of colon cancer. METHOD: We assessed the tumor growth inhibitory activity of HPRP-A1 with or without iRGD and 5FU on colon cancer in vitro and in vivo. In the in vitro part, we investigate the effect of HPRP-A1 alone and in combination with iRGD/5FU. RESULTS: Our results demonstrated that co-administration of HPRP-A1 with iRGD increased the apoptosis, while these two peptides in combination with 5FU increased the intracellular level of p53 that upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2. HPRP-A1 blocks the cell cycle progression in G0/G1. Co-administration of two peptides significantly reduced the size and weight of the tumors, while the group that received 5FU in combination with the peptides increased the necrotic and decrease the fibrotic area significantly in the tumor tissues, which also disrupt the oxidant/antioxidant balance. CONCLUSIONS: Our results indicated that HPRP-A1 could be considered an effective agent toward colon cancer in vitro and in vivo with the ability to enhance the effects of conventional chemotherapy agent 5FU.

The beneficial effect of combination therapy with sulfasalazine and valsartan in the treatment of ulcerative colitis.

Inflammatory bowel disease (IBD) is defined by the chronic inflammation of the digestive tract. Ulcerative colitis is one of the most prevalent chronic IBDs. The increase in the mucosal expression of angiotensin II (AT-II) in colitis suggests a possible role of AT-II in colitis-associated inflammation. Here, we examined the potential therapeutic effects of combination therapy regarding valsartan (Val), as an AT-II receptor blocker, with sulfasalazine (SSZ) in a murine colitis model. DSS induced colitis was initiated by the administration of dextran sodium sulfate (DSS) in male C57BL/6 mice for 1 week. Val (160 mg/kg/day, gavage) was given on the third day and continued for seven days. SSZ (100 mg/kg/day) was used as reference drug and also used in combination in one group (Val; 160 mg/kg/day and/or SSZ; 100 mg/kg/day). Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. The disease activity index in DSS-treated mice, including weight loss, stool consistency, and rectal bleeding, were significantly lower in the group of mice receiving the combination of valsartan and sulfasalazine compared to the DSS-treated group. Valsartan and sulfasalazine treatment was associated with a lower reduction in colon length, diminished colon weight, and high sensitivity C-reactive protein level in mice with DSS-induced colitis. Valsartan and sulfasalazine also reduced markers of oxidative stress after DSS administration. Our findings demonstrate the anti-inflammatory and anti-fibrotic activities of a combination therapy with sulfasalazine and valsartan in experimentally induced colitis, indicating its value as a potential therapeutic option for the treatment of colitis.

Bacteriotherapy in gastrointestinal cancer.

The most prevalent gastrointestinal (GI) cancers include colorectal cancer, stomach cancer, and liver cancer, known as the most common causes of cancer-related death in both men and women populations in the world. Traditional therapeutic approaches, including surgery, radiotherapy, and chemotherapy have failed in the effective treatment of cancer. Therefore, there is an urgent need for finding new effective anticancer agents. The available evidence and also the promising results of using bacteria as the anticancer agents on numerous cancer cell lines have attracted the attention of scientists for the therapeutic role of bacteria in the field of cancer therapy. Moreover, several studies on the bacteriotherapy agents have used genetic engineering to overcome the challenges and enhance the efficacy with the least drawbacks. Numerous bacterial species that can specifically target and internalize into the tumor cells are used live, attenuated, or genetically as compared to selectively consider the hypoxic condition of tumor, which results in the tumor suppression. The present study is a comprehensive review of the current literature on the use of bacteria and their substances such as bacteriocins and toxins in the treatment of different types of gastrointestinal cancers.

p28 Bacterial Peptide, as an Anticancer Agent.

Cancer remains a major cause of morbidity and mortality irrespective of the type of conventional chemotherapy. Therefore, there is an urgent need for new and effective anticancer therapeutic agents. Bacterial proteins and their derivative peptides appear as a promising approach for cancer treatment. Several, including an amphipathic, α-helical, 28-amino acid peptide derived from azurin, a 128-amino acid copper-containing redox protein secreted from Pseudomonas aeruginosa, show clinical promise in the treatment of adult and pediatric solid tumors. The peptide, p28, is a post-translational, multi-target anticancer agent that preferentially enters a wide variety of solid tumor cells. Mechanistically, after entry, p28 has two major avenues of action. It binds to both wild-type and mutant p53 protein, inhibiting constitutional morphogenic protein 1 (Cop1)-mediated ubiquitination and proteasomal degradation of p53. This results in increased levels of p53, which induce cell-cycle arrest at G2/M and an eventual apoptosis that results in tumor cell shrinkage and death. In addition, p28 also preferentially enters nascent endothelial cells and decreases the phosphorylation of FAK and Akt inhibiting endothelial cell motility and migration. Here, we review the current basic and clinical evidence suggesting the potential of p28 as a cancer therapeutic peptide.

Bacteria as a double-action sword in cancer.

Bacteria have long been known as one of the primary causative agents of cancer, however, recent studies suggest that they can be used as a promising agent in cancer therapy. Because of the limitations that conventional treatment faces due to the specific pathophysiology and the tumor environment, there is a great need for the new anticancer therapeutic agents. Bacteriotherapy utilizes live, attenuated strains or toxins, peptides, bacteriocins of the bacteria in the treatment of cancer. Moreover, they are widely used as a vector for delivering genes, peptides, or drugs to the tumor target. Interestingly, it was found that their combination with the conventional therapeutic approaches may enhance the treatment outcome. In the genome editing era, it is feasible to develop a novel generation of therapeutic bacteria with fewer side effects and more efficacy for cancer therapy. Here we review the current knowledge on the dual role of bacteria in the development of cancer as well as cancer therapy.

Bacteria and cancer: Different sides of the same coin.

Conventional cancer therapies such as chemotherapy, radiation therapy, and immunotherapy due to the complexity of cancer have been unsuccessful in the complete eradication of tumor cells. Thus, there is a need for new therapeutic strategies toward cancer. Recently, the therapeutic role of bacteria in different fields of medicine and pharmaceutical research has attracted attention in recent decades. Although several bacteria are notorious as cancer-causing agents, recent research revealed intriguing results suggesting the bacterial potential in cancer therapy. Thus, bacterial cancer therapy is an alternative anticancer approach that has promising results on tumor cells in-vivo. Moreover, with the aid of genetic engineering, some natural or genetically modified bacterial strains can directly target hypoxic regions of tumors and secrete therapeutic molecules leading to cancer cell death. Additionally, stimulation of immune cells by bacteria, bacterial cancer DNA vaccine and antitumor bacterial metabolites are other therapeutic applications of bacteria in cancer therapy. The present study is a comprehensive review of different aspects of bacterial cancer therapy alone and in combination with conventional methods, for improving cancer therapy.