Tuberculosis vaccine developments and efficient delivery systems: A comprehensive appraisal.

Despite the widespread use of the Bacillus Calmette-Guérin (BCG) vaccine, Mycobacterium tuberculosis (MTB) continues to be a global burden. Vaccination has been proposed to prevent and treat tuberculosis (TB) infection, and several of them are in different phases of clinical trials. Though vaccine production is in progress but requires more attention. There are several TB vaccines in the trial phase, most of which are based on a combination of proteins/adjuvants or recombinant viral vectors used for selected MTB antigens. In this review, we attempted to discuss different types of TB vaccines based on the vaccine composition, the immune responses generated, and their clinical trial phases. Furthermore, we have briefly overviewed the effective delivery systems used for the TB vaccine and their effectiveness in different vaccines.

Trends of fluoroquinolones resistance in Mycoplasma and Ureaplasma urogenital isolates: Systematic review and meta-analysis.

BACKGROUND: Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of antibiotic resistance and a continuous rise in resistance, the treatment options are limited, and treatment has become more challenging and costlier. OBJECTIVES: Therefore, this meta-analysis aimed to estimate worldwide resistance rates of genital Mycoplasmas and Ureaplasma to fluoroquinolones (ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin) agents. METHODS: We searched the relevant published studies in PubMed, Scopus, and Embase from until 3, March 2022. All statistical analyses were carried out using the statistical package R. RESULTS: The 30 studies included in the analysis were performed in 16 countries. In the metadata, the proportions of ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 59.8% (95% CI 49.6, 69.1), 31.2% (95% CI 23, 40), 7.3% (95% CI 1, 31), and 5.3% (95% CI 1, 2), respectively. According to the meta-regression, the ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin rate increased over time. There was a statistically significant difference in the fluoroquinolones resistance rates between different continents/countries (P < 0.05). CONCLUSIONS: Based on the results obtained in this systematic review and meta-analysis we recommend the use of the newer group of fluoroquinolones especially levofloxacin as the first choice for the treatment of genital mycoplasmosis, as well as ofloxacin for the treatment of genital infections caused by U. parvum.

The relationship between microbial contaminations of embryo transfer catheters with pregnancy outcome after embryo transfer.

Background: Different stages of assisted reproductive technologies are susceptible to contamination by various microorganisms. Objective: The aim of the study was to investigate the relationship between microbial contamination of embryo transfer catheters and the pregnancy outcome after embryo transfer. Methods: This cohort study was conducted on 60 patients candied for in vitro fertilization and embryo transfer cycles from 2021 to 2022. All embryos were transferred using a sterile syringe. The catheter contamination was checked by the microbial culture method, and in the case of microbial culture that were negative, polymerase chain reaction was done to confirm the result. The data analyzed using STATA 17 to determine the impact of catheter contamination on the clinical pregnancy rate. Results: The average age of peoples whose microbial culture was positive was lower than that of people whose microbial culture was negative (P<0.05). Also the results showed that people who live in villages have more positive microbial cultures than people who live in cities (P<0.05). Also there is no difference between the number of successful implantations and the pregnancy outcome between people whose microbial culture results were positive or negative. Conclusion: The results of the current study showed that the contamination of the embryo transfer catheter with microorganisms under our investigation did not affect the pregnancy outcome.

Tetracyclines resistance in Mycoplasma and Ureaplasma urogenital isolates derived from human: a systematic review and meta-analysis.

BACKGROUND: Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the treatment options are limited. OBJECTIVE: Therefore, this meta-analysis aimed to estimate resistance rates of genital Mycoplasmas to tetracyclines (tetracycline, doxycycline, and minocycline). METHODS: We searched the relevant published studies in PubMed, Scopus, and Embase until 3, March 2022. All statistical analyses were carried out using the statistical package R. RESULTS: The 26 studies included in the analysis were performed in 15 countries. In the metadata, the proportions of tetracycline, doxycycline, and minocycline resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 14.2% (95% CI 8.2-23.2%), 5% (95% CI 3-8.1%), and 11.9% (95% CI 6.3-21.5%), respectively. According to the meta-regression, the tetracycline and minocycline resistance rate decreased over time. Although, the doxycycline resistance rate increased over time. There was a statistically significant difference in the tetracyclines resistance rates between different continents/countries (P < 0.05). CONCLUSION: The prevalence rate and antibiotic susceptibility profiles vary geographically. Therefore, rigorous or improved antimicrobial stewardship, contact tracing, and enhanced intensive surveillance systems are necessitated for preventing the emergence and further spreading of tetracyclines resistance in genital Mycoplasmas.

Global status of Azithromycin and Erythromycin Resistance Rates in Neisseria gonorrhoeae: A Systematic Review and Meta-analysis.

Background: The widespread development of antibiotic resistance or decreased susceptibility in Neisseria gonorrhoeae (NG) infection is a global and significant human public health issue. Objectives: Therefore, this meta-analysis aimed to estimate worldwide resistance rates of NG to the azithromycin and erythromycin according to years, regions, and antimicrobial susceptibility testing (AST). Methods: We systematically searched the published studies in PubMed, Scopus, and Embase from 1988 to 2021. All analyses were conducted using Stata software. Results: The 134 reports included in the meta-analysis were performed in 51 countries and examined 165,172 NG isolates. Most of the included studies were from Asia (50 studies) and Europe (46 studies). In the metadata, the global prevalence over the past 30 years were 6% for azithromycin and 48% for erythromycin. There was substantial change in the prevalence of macrolides NG resistance over time (P <0.01). In this metadata, among 58 countries reporting resistance data for azithromycin, 17 (29.3%) countries reported that >5% of specimens had azithromycin resistance. Conclusions: The implications of this study emphasize the rigorous or improved antimicrobial stewardship, early diagnosis, contact tracing, and enhanced intensive global surveillance system are crucial for control of further spreading of gonococcal emergence of antimicrobial resistance (AMR).

Antibacterial activity of recently approved antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) strains: A systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates. METHODS: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0). RESULTS: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC50 and MIC90, (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC50 and MIC90, respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100). CONCLUSION: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future.

Antimicrobial resistance in Vibrio cholerae O1/O139 clinical isolates: a systematic review and meta-analysis.

OBJECTIVES: Vibrio cholerae O1/O139 is responsible for cholera epidemics that remains a huge public health menace across the globe. Furthermore, an increasing resistance rate among V. cholerae strains has been reported around the world. Therefore, the objective of this meta-analysis was to evaluate the weighted pooled resistance (WPR) rates in clinical V. cholerae O1/O139 isolates based on different years, areas, antimicrobial susceptibility testing, and resistance rates. RESEARCH DESIGN AND METHODS: We searched the studies in PubMed, Scopus, Embase, and Web of Science (until January 2020). Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 139 studies investigating 24,062 V. cholerae O1/O139 isolates were analyzed. The majority of the studies originated in Asia (n = 102). The WPR rates were as follows: azithromycin 1%, erythromycin 36%, ciprofloxacin 3%, cotrimoxazole 79%, doxycycline 7%, and tetracycline 20%. There was increased resistance to cotrimoxazole, ciprofloxacin, and tetracycline during the 1980-2020 years. CONCLUSIONS: Temporal changes in antibiotic resistance rate found in this study demonstrated the critical continuous surveillance of antibiotic resistance. Also, ciprofloxacin, azithromycin, gentamicin, cephalexin, imipenem, ofloxacin, and norfloxacin were found to be the best antibiotics against V. cholera, with the highest and the lowest effectiveness resistance rate.

Chitosan nanoparticles containing fusion protein (Hspx-PPE44-EsxV) and resiquimod adjuvant (HPERC) as a novel booster vaccine for Mycobacterium tuberculosis.

This study attempted to explore the immunogenicity of chitosan nanoparticles containing fusion protein (Hspx-PPE44-EsxV; HPE) and resiquimod adjuvant (HPERC) in BALB/c mice. HPE was initially expressed in E. coli BL21 cells. HPE and resiquimod adjuvant were then encapsulated in chitosan nanoparticles (HPERC). One group of mice were subcutaneously vaccinated on days 0, 14, and 28 with HPERC, and the other group was primed with bacilli Calmette-Guérin (BCG) on day 0 and then boosted with HPERC on days 14 and 28. Two weeks after the last injection, IFN-γ, IL-4, and IL-17 in spleen cell culture supernatants, and IgG2a and IgG1 titers in sera were measured. HPERC size was 130.84 ± 12.08 nm (n = 5). Zeta potential of HPERC was 29 ± 4 mv. The highest IFN-γ concentration was detected in BCG-primed mice that were boosted with HPERC. In addition, IL-17 production was significantly increased in all groups compared with that of control, except in those that received nanoparticle (NP), adjuvant (ADJ), NP/ADJ, and fusion protein (Hspx-PPE44-EsxV) (HPE). Comparison of IFN-γ and IL-4 concentration determined that Th1 was activated in BCG-primed and HPERC-boosted group in comparison to the other groups. No significant difference in concentration of IL-4 was observed between groups receiving HPERC and BCG-primed and HPERC-boosted group in comparison to group BCG. Concentrations of IgG2a and IgG1 also increased compared to the control group and the rate of IgG2a was higher compared to IgG1. Chitosan containing HPERC vaccine could induce a high level of specific cytokines in mice. The group of mice which first received BCG and then HPERC as booster vaccine could produce significant amounts of IFN-γ, IL-17, and IgG2a.

Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis.

BACKGROUND: Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance (HR)-the presence of resistant and susceptible isolates among MTB strains- has been reported from around the world. This phenomenon can lead to full resistance development and treatment failure. METHODS: We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until October 21, 2020). The study outcomes revealed the weighted pooled prevalence of antibiotic HR in MTB isolates with subgroup analysis by year, quality of study, and heteroresistance detection method. RESULTS: A total of 38 studies which had investigated MTB isolates were included in the meta-analysis. Geographically, the highest number of studies were reported from Asia (n = 24), followed by Africa (n = 5). Nineteen studies reported HR to isoniazid, with a weighted pooled prevalence of 5% (95% CI 0-12) among 11,761 MTB isolates. Also, there is no important trend for the subgroup analysis by the study period (2001-2014 vs 2015-2017 vs 2018-2020). HR to rifampin was reported in 17 studies, with a weighted pooled prevalence of 7% (95% CI 2-14) among 3782 MTB isolates. HR to fluoroquinolone and ethambutol were reported in 12 and 4 studies, respectively, with weighted pooled prevalence of 10% and 1% among 2153 and 1509 MTB isolates, correspondingly. CONCLUSION: Based on our analysis, HR in MTB isolates with different frequency rate is present worldwide. Thus, the selection of appropriate and reliable methods for HR detection is crucial for TB eradication.

Cyclin-dependent kinase inhibitors (CDKIs) and the DNA damage response: The link between signaling pathways and cancer.

At the cellular level, DNA repair mechanisms are crucial in maintaining both genomic integrity and stability. DNA damage appears to be a central culprit in tumor onset and progression. Cyclin-dependent kinases (CDKs) and their regulatory partners coordinate the cell cycle progression. Aberrant CDK activity has been linked to a variety of cancers through deregulation of cell-cycle control. Besides DNA damaging agents and chromosome instability (CIN), disruptions in the levels of cell cycle regulators including cyclin-dependent kinase inhibitors (CDKIs) would result in unscheduled proliferation and cell division. The INK4 and Cip/Kip (CDK interacting protein/kinase inhibitor protein) family of CDKI proteins are involved in cell cycle regulation, transcription regulation, apoptosis, and cell migration. A thorough understanding of how these CDKIs regulate the DNA damage response through multiple signaling pathways may provide an opportunity to design efficient treatment strategies to inhibit carcinogenesis.

Clinical, epidemiological, laboratory, and radiological characteristics of novel Coronavirus (2019-nCoV) in retrospective studies: A systemic review and meta-analysis.

BACKGROUND: In December 2019, a novel pneumonia related to the 2019 coronavirus unexpectedly developed in Wuhan, China. We aimed to review data of the novel Coronavirus (2019-nCoV) by analyzing all the published retrospective studies on the clinical, epidemiological, laboratory, and radiological characteristics of patients with 2019-nCoV. METHODS: We searched in four bibliographic databases PubMed, Scopus, Embase, and Web of Science) for studies March 10, 2020 focused on the clinical, epidemiological, laboratory, and radiological characteristics of patients with 2019-nCoV for meta-analysis. The Newcastle-Ottawa Scale was used to quality assessment, and publication bias was analyzed by Egger's test. In the meta-analysis, a random-effects model with Stata/SE software, v.14.1 (StataCorp, College Station, TX) was used to obtain a pooled incidence rate. RESULTS: Fifty studies were included in this systematic review and meta-analysis with 8815 patients and the mean age was 46 years and 4647 (52.7%) were male. The pooled incidences rate of clinical symptoms were: fever (83%, 95% CI: 0.77, 0.89), cough (59%, 95% CI: 0.48, 0.69), myalgia or fatigue (31%, 95% CI: 0.23, 0.39), sputum production (29%, 95% CI: 0.21, 0.39), and dyspnea (19%, 95% CI: 0.12, 0.26). The pooled incidence rate of acute respiratory distress syndrome (ARDS) was (22%, 95% CI: 0.00, 0.60). CONCLUSION: The results of this systemic review and meta-analysis present a quantitative pooled incidence rate of different characters of 2019-nCoV and has great potential to develop diagnosis and patient's stratification in 2019-nCoV. However, this conclusions of this study still requisite to be warranted by more careful design, larger sample size multivariate studies to corroborate the results of this meta-analysis.

The potential use of theranostic bacteria in cancer.

Conventional chemotherapy approaches have not been fully successful in the treatment of cancer, due to limitations imposed by the pathophysiology of solid tumors, leading to nonspecific drug uptake by healthy cells, poor bioavailability, and toxicity. Thus, novel therapeutic modalities for more efficient cancer treatment are urgently required. Living bacteria can be used as a theranostic approach for the simultaneous diagnosis and therapy of tumors. Herein, we summarize the currently available literature focused on the advantages and challenges for the use of theranostic bacteria in cancer therapy.

CRISPR/Cas9 novel therapeutic road for the treatment of neurodegenerative diseases.

CRISPR (clustered regularly interspaced short palindromic Repeats)/Cas9 is a new genetic editing technology that can be a beneficial method to advance gene therapy. CRISPR technology is a defense system of some bacteria against invading viruses. Genome editing based on the CRISPR/Cas9 system is an efficient and potential technology that can be a viable alternative to traditional methods. This system is a compound of a short guide RNAs (gRNAs) for identifying the target DNA sequence and Cas9 protein as nuclease for breaking and cutting of DNA. In this review, recent advances in the CRISPR/Cas9-mediated genome editing tools are presented as well as their use in gene therapy strategies for the treatment of neurological disorders including Parkinson's disease, Alzheimer's disease, and Huntington's disease.

Inhibitory effect of isolated Lactobacillus from oral cavity against bacterial Pathogens and its effect on health promotion / Efecto inhibidor de Lactobacillus aislado de la cavidad oral contra patógenos bacterianos y su efecto en la promoción de la salud

Aims: To determine the inhibitory effect of oral Lactobacillus against bacterial pathogens and investigate correlation between presence of Lactobacillus strains and health promotion. Method: One hundred saliva samples were collected from oral cavity of domestic dairy consumers and were investigated for the isolation and identification of Lactobacillus strain by conventional culture and sequencing of 16SrRNA. Furthermore, well diffusion assay was performed to determination of antibacterial activity of Lactobacillus strains against bacterial pathogens including Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis and Enterococcus faecium. Finally, association between health condition and isolation of Lactobacillus were investigated and obtained data using questionary form were analysed by chi-square test. Results: Thirty Lactobacillus strains recovered from 100 hundred saliva samples. The most common isolated strain was L. gasseri (n=18) and followed by L. vaginalis (n=3) and L. salivarius (n=3). All Lactobacillus strains demonstrated antibacterial activity against at least one of the investigated pathogens. However, the strongest results were obtained by L. vaginalis against K. pneumonia. The correlation between the presence of thirty Lactobacillus strains and health promotion not found. However, only L. gasseri species has significant positive impact on health in their hosts (P < 0.05). Conclusion: Only some Lactobacillus species have a positive impact on health promotion. Despite of weak activity against the investigated pathogens, L. gasseri has a positive impact on the mental problem (intense anger and depression) of their hosts

Objetivos: Determinar el efecto inhibidor del Lactobacillus aislado de la cavidad oral contra patógenos bacterianos e investigar la correlación entre la presencia de cepas de Lactobacillus y la promoción de la salud. Método: se recolectaron cien muestras de saliva de la cavidad oral de consumidores de productos lácteos y se investigó el aislamiento e identificación de la cepa de Lactobacillus mediante cultivo convencional y secuenciación de 16SrRNA. Además, se realizó un ensayo de difusión en pocillos para determinar la actividad antibacteriana de las cepas de Lactobacillus contra patógenos bacterianos que incluyen Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis y Enterococcus faecium. Finalmente, se investigó la asociación entre el estado de salud y el aislamiento de Lactobacillus y se obtuvieron los datos utilizando el cuestionario mediante la prueba de chi-cuadrado. Resultados: Se aislaron treinta cepas de Lactobacillus de 100 muestras de saliva. La cepa aislada más común fue L. gasseri (n = 18), seguida por L. vaginalis (n = 3) y L. salivarius (n = 3). Todas las cepas de Lactobacillus demostraron actividad antibacteriana contra al menos uno de los patógenos investigados Sin embargo, los resultados más fuertes fueron obtenidos por L. vaginalis contra K. pneumonia. No se encontraron correlación entre la presencia de algunas de las treinta cepas de Lactobacillus y la promoción de la salud. Sin embargo, solo la especie L. gasseri tuvo un impacto positivo significativo en la salud de sus hospedadores (P <0,05). Conclusión: solo algunas especies de Lactobacillus tienen un impacto positivo en la promoción de la salud. A pesar de la actividad débil contra los patógenos investigados, L. gasseri tiene un impacto positivo en el problema mental (ira intensa y depresión) de sus huéspedes

CRISPR/Cas9 technology as a potent molecular tool for gene therapy.

Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR-Cas9) is an RNA-guided gene editing tool which offers several advantageous characteristics in comparison with the conventional methods (e.g., zinc finger nucleases and transcription activator-like effector nucleases) such as cost-effectiveness, flexibility, and being easy-to-use. Despite some limitations such as efficient delivery and safety, CRISPR-Cas9 is still the most convenient tool for gene editing purposes. Due to the potential capability of the CRISPR-Cas9 system in genome editing and correction of casual mutations, it can be considered as a possible therapeutic system in the treatment of disorders associated with the genome mutations and in particular cancer treatment. In this review, we will discuss CRISPR-Cas-based gene editing along with its classifications and mechanism of action. Furthermore, the therapeutic application of the CRISPR-Cas9 system in mutational disorders, delivery systems, as well as its advantages and limitations with a special emphasis on cancer treatment will be discussed.

Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein.

The cell cycle is controlled by precise mechanisms to prevent malignancies such as cancer, and the cell needs these tight and advanced controls. Cyclin dependent kinase inhibitor p27 (also known as KIP1) is a factor that inhibits the progression of the cell cycle by using specific molecular mechanisms. The inhibitory effect of p27 on the cell cycle is mediated by CDKs inhibition. Other important functions of p27 include cell proliferation, cell differentiation and apoptosis. Post- translational modification of p27 by phosphorylation and ubiquitination respectively regulates interaction between p27 and cyclin/CDK complex and degradation of p27. In this review, we focus on the multiple function of p27 in cell cycle regulation, apoptosis, epigenetic modifications and post- translational modification, and briefly discuss the mechanisms and factors that have important roles in p27 functions.