Helicobacter pylori antigens as immunomodulators of immune system.

Helicobacter pylori (H. pylori) is one of the most prevalent human pathogens and the leading cause of chronic infection in almost half of the population in the world (~59%). The bacterium is a major leading cause of chronic gastritis, gastric and duodenal ulcers, and two type of malignancies, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Despite the immune responses mounted by the host, the bacteria are not cleared from the body resulting in a chronic infection accompanied by a chronic inflammation. Herein, a review of the literature discussing H. pylori antigens modulating the immune responses is presented. The mechanisms that are involved in the modulation of innate immune response, include modulation of recognition by pattern recognition receptors (PRRs) such as modulation of recognition by toll like receptors (TLR)4 and TLR5, modulation of phagocytic function, and modulation of phagocytic killing mediated by reactive oxygen species (ROS) and nitric oxide (NO). On the other hands, H. pylori modulates acquired immune response by the induction of tolerogenic dendritic cells (DCs), modulation of apoptosis, induction of regulatory T cells, modulation of T helper (Th)1 response, and modulation of Th17 response.

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

Radioprotective Potency of Nanoceria.

Cancer presents a significant medical challenge that requires effective management. Current cancer treatment options, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy, have limitations in terms of their efficacy and the potential harm they can cause to normal tissues. In response, researchers have been focusing on developing adjuvants that can enhance tumor responses while minimizing damage to healthy tissues. Among the promising options, nanoceria (NC), a type of nanoparticle composed of cerium oxide, has garnered attention for its potential to improve various cancer treatment regimens. Nanoceria has demonstrated its ability to exhibit toxicity towards cancer cells, inhibit invasion, and sensitize cancer cells to both radiation therapy and chemotherapy. The remarkable aspect is that nanoceria show minimal toxicity to normal tissues while protecting against various forms of reactive oxygen species generation. Its capability to enhance the sensitivity of cancer cells to chemotherapy and radiotherapy has also been observed. This paper thoroughly reviews the current literature on nanoceria's applications within different cancer treatment modalities, with a specific focus on radiotherapy. The emphasis is on nanoceria's unique role in enhancing tumor radiosensitization and safeguarding normal tissues from radiation damage.

Immune escape strategies of Pseudomonas aeruginosa to establish chronic infection.

The infection caused by P. aeruginosa still is dangerous throughout the world. This is partly due to its immune escape mechanisms considerably increasing the bacterial survival in the host. By escape from recognition by TLRs, interference with complement system activation, phagocytosis inhibition, production of ROS, inhibition of NET production, interference with the generation of cytokines, inflammasome inhibition, reduced antigen presentation, interference with cellular and humoral immunity, and induction of apoptotic cell death and MDSc, P. aeruginosa breaks down the barriers of the immune system and causes lethal infections in the host. Recognition of other immune escape mechanisms of P. aeruginosa may provide a basis for the future treatment of the infection. This manuscript may provide new insights and information for the development of new strategies to combat P. aeruginosa infection. In the present manuscript, the escape mechanisms of P. aeruginosa against immune response would be reviewed.

Evaluation of the inhibitory effects of TiO2 nanoparticle and Ganoderma lucidum extract against biofilm-producing bacteria isolated from clinical samples.

The emergence of multidrug-resistant pathogens leads to treatment failure. So, the need for new antibacterial drugs is urgent. We evaluated the antibacterial and antibiofilm effects of titanium dioxide (TiO2) nanoparticles (NPs) and Ganoderma extract against biofilm-producing Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) by microbroth dilution and crystal violet assays. The combined effect of these compounds was studied using the checkerboard method. The OD260 was measured to assess the destruction of the membrane permeability. The expression of biofilm-related genes (iacA and algD) was investigated by real-time PCR. MRSA isolate was more susceptible to test compounds. The OD260 increased and algD gene was down-regulated after treatment with TiO2 NPs and a combination of TiO2 NPs and Ganoderma extract. iacA gene did not affect by test compounds. Overall, these findings revealed that nanoparticles and natural substances might represent the potential candidates to develop promising antibacterial agents, especially against Gram-positive bacteria.

Designing a novel fusion protein from Streptococcus agalactiae with apoptosis induction effects on cervical cancer cells.

Cervical cancer remains life-threatening cancer in women around the world. Due to the limitations of conventional treatment approaches, there is an urgent need to develop novel and more efficient strategies against cervical cancer. Therefore, the researchers attend to the alternative anti-cancer compounds like bacterial products. Rib and α are known as surface proteins of Streptococcus agalactiae with immunologic effects. In the present study, we designed a new anti-cancer fusion protein (Rib-α) originating from S. agalactiae with in silico methods, and then, the recombinant gene was cloned in the pET-22 (+) expression vector. The recombinant protein was expressed in E. coli BL21. To purify the expressed protein, we applied the Ni-NTA column. The molecular mechanism by which Rib-α is cytotoxic to cancer cells has been discussed based on MTT, flow cytometry, and real-time PCR methods. The engineered fusion protein suppressed the proliferation of the cancer cells at 180 µg/ml. Cytotoxic assessment and morphological changes, augmentation of apoptotic-related genes, upregulation of caspase-3 mRNA, and flow cytometric analysis confirmed that apoptosis might be the principal mechanism of cell death. According to our findings, Rib-α fusion protein motivated the intrinsic apoptosis pathway. Therefore, it can be an exciting candidate to discover a new class of antineoplastic agents.

Molecular typing of clinical and environmental isolates of Klebsiella pneumoniae producing ESBLs by PFGE.

Objectives: Klebsiella pneumoniae is the common cause of pneumonia in hospitalized patients, particularly in intensive care units (ICU). The infection can transfer by medical equipment such as mechanical ventilators. This study aimed to investigate the molecular typing of the extended-spectrum beta-lactamase-producing K. pneumoniae isolates recovered from Beheshti Hospital, Kashan, Iran. Materials and Methods: K. pneumoniae isolates producing ESBLs have been collected from the samples obtained from Shahid Beheshti hospital, Kashan, Iran. Antimicrobial susceptibility was determined using the Kirby Bauer disk diffusion method. The presence of ESBLs was evaluated using CLSI for ESBL screening by the double-disk diffusion method. Molecular typing was conducted by pulsed-field gel electrophoresis (PFGE). In total, 89 K. pneumoniae isolates were recovered, of which 47.1% were ESBL producers. Results: Results showed that all of the clinical and environmental isolates were resistant to ceftriaxone, meropenem, cefazolin, cefotaxime, cephalothin, and piperacillin-tazobactam. All isolates were grouped under four clusters (A-D). The major cluster was related to the C cluster with 22 isolates (19 clinical and 3 environmental). Seventy-two percent of isolates were from the ICU ward. There was no correlation between antibiotic resistance patterns and PFGE clusters (P=0.2). Conclusion: We observed a common molecular signature among both clinical and environmental K. pneumoniae isolates, indicating a similar genotype and likely a common origin for ESBL producer isolates found in different hospital wards. Therefore, hospitals need to implement an effective infection control system to decrease the spreading of ESBL strains within the hospitals and subsequently the transmission of the infection to patients.

Streptococcal bacterial components in cancer therapy.

The incidence rate of cancer is steadily increasing all around the world, and there is an urgent need to develop novel and more effective treatment strategies. Recently, bacterial therapy has been investigated as a new approach to target cancer, and is becoming a serious option. Streptococcus strains are among the most common and well-studied virulent bacteria that cause a variety of human infections. Everyone has experienced a sore throat during their lifetime, or has been asymptomatically colonized by streptococci. The ability of Streptococcus bacteria to fight cancer was discovered more than 100 years ago, and over the years has undergone clinical trials, but the mechanism is not yet completely understood. Recently, several animal models and human clinical trials have been reported. Streptococcal strains can have an intrinsic anti-tumor activity, or can activate the host immune system to fight the tumor. Bacteria can selectively accumulate and proliferate in the hypoxic regions of solid tumors. Moreover, the bacteria can be genetically engineered to secrete toxins or enzymes that can specifically attack the tumors.

Genetic Diversity, Antimicrobial Resistance Pattern, and Biofilm Formation in Klebsiella pneumoniae Isolated from Patients with Coronavirus Disease 2019 (COVID-19) and Ventilator-Associated Pneumonia.

INTRODUCTION: Patients with acute respiratory distress syndrome caused by coronavirus disease 2019 (COVID-19) are at risk for superadded infections, especially infections caused by multidrug resistant (MDR) pathogens. Before the COVID-19 pandemic, the prevalence of MDR infections, including infections caused by MDR Klebsiella pneumoniae (K. pneumoniae), was very high in Iran. This study is aimed at assessing the genetic diversity, antimicrobial resistance pattern, and biofilm formation in K. pneumoniae isolates obtained from patients with COVID-19 and ventilator-associated pneumonia (VAP) hospitalized in an intensive care unit (ICU) in Iran. METHODS: In this cross-sectional study, seventy K. pneumoniae isolates were obtained from seventy patients with COVID-19 hospitalized in the ICU of Shahid Beheshti hospital, Kashan, Iran, from May to September, 2020. K. pneumoniae was detected through the ureD gene. Antimicrobial susceptibility testing was done using the Kirby-Bauer disc diffusion method, and biofilm was detected using the microtiter plate assay method. Genetic diversity was also analyzed through polymerase chain reaction based on enterobacterial repetitive intergenic consensus (ERIC-PCR). The BioNumerics software (v. 8.0, Applied Maths, Belgium) was used for analyzing the data and drawing dendrogram and minimum spanning tree. Findings. K. pneumoniae isolates had varying levels of resistance to antibiotics meropenem (80.4%), cefepime-aztreonam-piperacillin/tazobactam (70%), tobramycin (61.4%), ciprofloxacin (57.7%), gentamicin (55.7%), and imipenem (50%). Around 77.14% of isolates were MDR, and 42.8% of them formed biofilm. Genetic diversity analysis revealed 28 genotypes (E1-E28) and 74.28% of isolates were grouped into ten clusters (i.e., clusters A-J). Clusters were further categorized into three major clusters, i.e., clusters E, H, and J. Antimicrobial resistance to meropenem, tobramycin, gentamicin, and ciprofloxacin in cluster J was significantly higher than cluster H, denoting significant relationship between ERIC clusters and antimicrobial resistance. However, there was no significant difference among major clusters E, H, and J respecting biofilm formation. CONCLUSION: K. pneumoniae isolates obtained from patients with COVID-19 have high antimicrobial resistance, and 44.2% of them have genetic similarity and can be clustered in three major clusters. There is a significant difference among clusters respecting antimicrobial resistance.

Chitosan-based nanoparticles against bacterial infections.

Chitosan nanomaterials have become a hot topic in biomedicine due to exerting antimicrobial effects with interestingly high levels of biodegradability and biocompatibility without causing toxicity. Regarded as a potential means of wound dressing with antimicrobial activity, chitosan exhibits higher efficiency when it is functionally modified with other natural compounds, metallic antimicrobial particles and antibiotics. Mechanistically, the antibacterial effect of chitosan is mostly, associated with the death-proceeding leakage of intracellular content, induced by malfunction and altered permeability of the negatively charged cell membrane, on which chitosan is adsorbed. Moreover, chitosan nanoparticles (NPs) are endowed with favorable features of NPs (i.e., large surface-to-volume ratio, high functionalization possibilities and a greater capacity for drug loading), as well as that of their chitosan base, thereby possessing strengthened antibacterial potential. In addition, polycations target negatively charged bacterial membranes, so bacteria cells are more strongly affected by polycationic chitosan NPs than pure chitosan.