Antibiotics, one of the miracle discoveries of the 20^th century after world war revolutionized the treatment and prophylaxis of infectious diseases. Antibiotics led to an increase in the quality of health-care system but with the emergence of antibiotic-resistant bacterial strains compromised their very potential. The WHO calls bacterial resistance as one of the major threats to global health, food security, and development today. Antibiotic resistance poses a need of alternative therapy to conventional antibiotics. As proved in preantibiotic era phage therapy is effective against a number of successful pathogens and can be used as an alternative strategy to restrain stern infections such as antibiotic resistance tuberculosis (TB). In the present paper, effectiveness of phage therapy and use of model organisms for developing treatment strategy for antibiotic-resistant TB is discussed so as to explore new possibilities in battle against antibiotic resistance.

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The aim of this study is well stated to address in recent advances on probiotics in the past 50 years. Probiotics are the living cell organisms. It is a presence in human and animal gut. The probiotic organisms are natural antibiotics in the human-animal gut. This reviews the main role mechanisms of action in probiotics such as probiotics are antibiotics, probiotics in antibacterial activity, probiotic action in fish gut bacteria, dietary supplements of probiotics, gastrointestinal microbiota of fishes, microbial community of the gastrointestinal tract of fish, bioactive compounds from probiotic bacteria, probiotic uses in cancer therapeutic applications, and applications of probiotics. The most common probiotics are used in many ways such as boosting the immune system, inhibition of pathogenic organism, prevention of cancer, reduction of inflammatory bowel disease, reducing cholesterol level, and synthesis of Vitamin A. Nowadays, food products are mainly involved in chemical preservatives. These preservative agents are causing the disease to affect the human health. The probiotic food products are used to the development of human-animal health.

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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 (PM_2.5) 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 PM_2.5(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 PM_2.5 and CO was positively associated with TB development.

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Proteins are composed of linear chains of amino acids that form a unique three-dimensional structure in their native environment. Such native structure favors the proteins to perform their biochemical activity. Protein is formed of some levels of structure. The primary structure of a protein is specified by the particular amino acid sequence. In an amino acid sequence, patterns of local bonding can be identified as secondary structure. The final level that forms a tertiary protein structure is composed of the mentioned elements and form after the protein folds into its native state. To find the native structure of proteins, the physicochemical principles as well as identifying the lowest free-energy states are considered as the best properties and to predict target proteins with unknown structures, the bioinformatics-based methods have earned considerable success. Protein structure prediction methods have been mainly classified into three types: ab Initio folding, comparative (homology) modeling and threading. Each mentioned method may be applied for a protein structure, depending on the existence of related experimental structures that are deposited in the PDB. Once an initial model is generated, refinement simulations are conducted to reassemble the global topology and the local structures of the protein chains. Since significant features of a model may be in regions that are structurally distinct from the template, refining of a primary model is influential. A trustful strategy is included a stereo-chemical check and discovering how the model deviates from the basic disciplines of known experimental structures.

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Background: Recently, the nanoparticle (NP) application in many fields of medicine due to their specific physical and chemical properties has been developed. Therefore, especially in vivo evaluation of their toxicity is necessary. The aim of this study was to compare the toxicity of Fe₃O₄NPs coated with biocompatible compounds and uncoated NPs. Methods: Wetted chemical method (or wet chemical method) was used to synthesize Fe₃O₄NPs. The synthesized NPs were coated with chitosan and the coating interactions were investigated by Fourier-transform infrared spectroscopy. The magnetic and structural properties of Fe₃O₄and coated Fe₃O₄NPs were evaluated by transmission electron microscope and X-ray diffraction. The toxicity assessment of Fe₃O₄and coated Fe₃O₄NPs was studied in mice by intraperitoneal injections during the 1-month period. Antioxidant enzyme glutathione peroxidase (GPX), malondialdehyde, and low-density lipoprotein/high-density lipoprotein were measured 15 and 30 days after injection. Results: The synthesized NPs have a single phase and spinal structure and their size distribution in the net form is 5–10 nm. Some factors were changed due to the injection of both uncoated and coated NPs. The all-used concentration of chitosan-coated Fe₃O₄NPs could increase the GPX enzyme activity. The Fe₃O₄NPs can reduce the GPX enzyme activity in high concentration (50 mg/kg, 100 mg/kg, and 150 mg/kg). Conclusion: The results indicated that NPs based on their dosage and body condition can induce toxicity effects in the body. It should be mentioned that the chitosan-coated ones can decrease their effects.

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Background: Copper is a pollutant compound which can cause earnest toxicity in human and some organisms. Bioreporters are frugal and non-toxic detectors for pollution compounds. Precedent designed recombinant Escherichia coli copper bioreporters with the lux gene of Vibrio fischeri or Aequorin luciferase of Jellyfish does not provide a high sensitivity. The aim of current study was to design an incipient Copper bioreporter with applying firefly luciferase and Copper resistance promoter of P. syringae pv.Tomato in Escherichia coli XL1-Blue. Methods: Recombinant pGL3 was obtained by applying the pGL3-Control vector to Escherichia coli XL1-Blue, by Polymerase Chain Reaction method and double digestion. Recombinant Escherichia coli cells were cultured with applying different concentrations of copper sulphate to study the activity of luciferase by Luminometer. Copper bioreporter specificity was resolute by different concentrations of Zinc sulfate and Ferric sulfate. Results: Recombinant Escherichia coli BL21, with copper promoter gene in pGL3 Vector showed the highest Luciferase activity in 0.1 millimolar of Copper sulfate. The highest Luciferase activity was in 0.09 millimolar and 1.0 millimolar of Zinc sulfate and Ferric sulfate respectively. Conclusion: Current study provided a categorical bioreporter for detecting copper, utilizing firefly luciferase with a high specificity (96.1%). By optimizing inhibitor factors, application of current copper bioreporter can be developed in human life.

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Tuberculosis (TB) remains the major health problem causing morbidity and mortality throughout the world. Increase in multidrug resistant, extensively drug-resistant, and totally drug-resistant cases of tuberculosis are causing concern to the health administrators of TB control programs. In spite of tremendous research on drug targets and drugs in TB, no new drug which is safer and more effective, has come out. This mini-review focuses on different important drug targets in Mycobacterium tuberculosis reported and emphasizes the urgency for new drug development and integrative approach for successful control of TB.

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Background: The most practical test for identifying tuberculosis (TB) in developing countries remains smear microscopy. However, due to its low sensitivity, a new point-of-care diagnostic method has been developed. The purpose of this study was to assess the performance of TB-Loop-mediated isothermal amplification (TB-LAMP) test on sputum samples of suspected TB cases. Methods: Suspected pulmonary TB patients (527) from Jamot Hospital and without any history of anti-TB treatment were consecutively included in the study. Smear microscopy, TB-LAMP, GeneXpert® MTB/RIF, and liquid culture using BACTEC 960 Mycobacteria Growth Indicator Tube (MGIT) were performed on sputum samples collected from these patients. The sensitivity and specificity of TB-LAMP were compared with smear microscopy and GeneXpert® MTB/RIF. MGIT culture was the gold standard. Results: TB-LAMP and smear microscopy showed sensitivities of 82.6% (95% confidence interval [CI], 76.9–87.2) and 53.6% (95% CI, 46.8–60.3), respectively, and specificities of 96.0% (95% CI, 93.2–97.7) and 99.0% (95% CI, 97.1–99.7), respectively. The sensitivity and specificity of TB-LAMP were similar to GeneXpert®, (89.9%; 95% CI, 85.0–93.3 and 97.0%; 95% CI, 94.4–98.4). Conclusion: TB-LAMP is more sensitive than currently used microscopy. It presents a favorable diagnostic tool for TB in peripheral laboratories with limited equipment, such as those in developing countries.

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Background: Irrigants plays a vital role in disinfection of the root canal system. Although concentration dependent, a fine balance between antimicrobial efficacy and biocompatibility need to be maintained at all times. The aim of the present study was to evaluate the cytotoxicity of conventional irrigants on two different cell lines in a dose-dependent manner in vitro. Methods: Sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), and iodine potassium iodide (IKI) were prepared in concentrations of 5%, 2.5%, 2%, and 1%. About 0.9% saline served as negative control and Biopure MTAD^TM (100%) as positive control. Permanent (Henrietta Lacks [HeLa]) and primary (human gingival fibroblast [HGF]) cell lines were chosen to evaluate the cytotoxicity of the irrigants by trypan blue assay. A volume of 30 μl of the cell suspension was treated with 20 μl of irrigants. The cell suspension was loaded into Neubauer chamber after 5 min, and cell count was performed under inverted microscope and expressed as viability percentage. Results: NaOCl at all concentrations was cytotoxic on both cell lines; MTAD on HeLa had nonviable scores with limited viability on HGF. Only 1% IKI had better viability than higher concentrations. Although 1% CHX had higher viability on both cell lines, bactericidal concentration of 2% CHX showed promising results. Conclusion: Target cell line (HGF) appears to be more sensitive than the use of nontarget cell line (HeLa) for evaluating cytotoxicity. NaOCl and MTAD were cytotoxic and should be used with caution. Lower concentrations of CHX appear to be less cytotoxic than any irrigant and concentrations tested.

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There has been an increased use of cardiac pacemaker device utilization in cardiac patients with a corresponding increase of device-related infections in these patients. The common cause of postpacemaker implantation infection is either Gram-positive or Gram-negative bacteria. Infection of pacemaker implantation site due to nontuberculous mycobacteria is rare. Globally, thirty-two cases of pacemaker device infections caused by nontuberculous mycobacteria were reported. It is important to carry out not only species identification of mycobacteria but also drug susceptibility testing to start precise treatment to those patients, who are infected with atypical mycobacteria. We report a patient with pacemaker pocket infection due to Mycobacterium chelonae.

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Background: Viral flu is the predominant cause of hospitalization in young children, which invariably leads to enhanced morbidity and mortality in children in developing countries. Initial treatment of viral flu is based on presumptive diagnosis. Bedside testing is not common in clinical settings because of variable sensitivity and specificity of rapid tests in different settings. Methods: To address this issue, we evaluated the performance of Binax influenza A/B rapid testing kit against two robust molecular platforms (quantitative real-time polymerase chain reaction [qRT-PCR] and TaqMan array card [TAC]) in 24 nasopharyngeal (NP) swabs, collected from children under 5 years of age. Results: Binax was found to be less sensitive (56%), but 100% specific compared to qRT-PCR (100%) and TAC (>100%). Using TAC cards, 75% of samples were found to be coinfected with other bacterial and viral targets. Conclusion: Binax flu is suitable for bedside testing in clinical and community settings. The negative results of Binax should be interpreted with caution and confirmed by rapid molecular tests.

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Background: There is a wide variation in existing Mycobacterium tuberculosis strains across the globe, and false results in line probe assay (LPA) can occur due to the presence of unique genetic mutations in different settings. Objectives: An attempt was made to observe uncommon mutations in multidrug-resistant tuberculosis (MDR-TB) strains and determination of genetic diversity by spoligotyping and to study the treatment outcome in patients with uncommon mutations. Materials and Methods: Band pattern analysis of LPA strips was performed as per manufacturer's instructions. DNA sequencing was performed to confirm the presence of uncommon mutations in Intermediate Reference Laboratory in Delhi state. Results: Four uncommon mutations were recognized along with 12 unique spoligotype patterns which serve as an update to worldwide databases. The noteworthy presence of a spoligotype previously rarely seen in India was the SIT53/T1 pattern. Central Asian (CAS) spoligotype was highly associated with MDR followed by Beijing type. During follow-up, the treatment outcomes of cases showing uncommon mutations were considered as cured, after completion of their treatment. Conclusion: The rifampicin resistance appears to be an effective marker of MDR-TB. The presence of uncommon mutations confirms genetic polymorphism that may require treatment targeted at both drug-resistant and drug-susceptible phenotypes for the better management of patients with MDR-TB.

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Background: Tuberculosis (TB) still remains the leading cause of death worldwide and was unanswered till date. Available treatment strategies have many drawbacks such as longer treatment period, side effects, and drug interactions, which result in patient noncompliance. In the present work, we thrived to develop inhibitors against unexplored key target glutamate racemase. Methods: Lead was identified from in-house database using differential scanning fluorimetry, inhibitors were developed by lead derivatization technique and evaluated them by various biological assays. Results: In oxoquinazoline series, compounds 18 (10.1 ± 0.62 μM) and 22 (5.23 ± 0.34 μM) were found to be the most promising potent inhibitors among all. These compounds also showed their inhibition on replicating and nonreplicating bacteria. Conclusion: Our attempt to develop the potent novel inhibitors against Mycobacterium tuberculosis resulted in developing few promising inhibitors, yet these compounds need further studies to answer all questions in drug discovery. Further optimization of compounds can result in still better compounds for treating TB.

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Background: Levamisole at high concentrations has been shown to have anticancer and immunosuppressive actions. Methods: In the present study, fate of levamisole in cell culture and 3 H-levamisole binding to murine splenic lymphocytes, normal and malignant human lymphocytes has been investigated. Results: High-performance liquid chromatography analysis of cell culture supernatants of myeloma cells treated with levamisole has shown that products of levamisole appeared with progressive culture period indicating a metabolic transformation. 3 H-levamisole binding assays indicate that the binding was signifi cantly higher in lysates of lipopolysaccharide-stimulated murine splenic lymphocytes as compared to whole cells. Conclusion: The degradation of levamisole could be one more possible reason for the high concentration of levamisole required to get the desirable cytotoxic effect on myeloma cells.

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