Pronounced dysbiosis in the gut microbiome is common among sepsis patients, resulting in aggravation of the disease. This disturbance not only impacts gut integrity but also initiates localized immune responses that may progress to systemic inflammation. This review explores recent discoveries regarding the dysregulation of the gut microbiome, alterations in gut permeability, and disruptions in intestinal immune responses that occur during sepsis. In addition, we discuss innovative therapeutic strategies, encompassing the impacts of metabolites derived from microbes, the selection of beneficial probiotics, and the utilization of fecal microbiota transplantation in the management of sepsis. Understanding the complexities of the gut microbiome holds the promise of revealing novel strategies that may transform the treatment of sepsis, providing a ray of hope for improved outcomes in critically ill patients.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and disabling disease related to persistent fatigue, exercise intolerance, post-exertional malaise, cognitive dysfunction, and musculoskeletal/joint pain. Gastrointestinal comorbidities, including irritable bowel syndrome, have been reported in affected individuals, indicating a potential role of gut microbiota in disease progression. In this paper, bacterial and metabolomic dysbiosis in subjects with ME/CFS are reviewed, and phenotypic, microbial, and metabolic biomarkers specific to individual cohorts are also identified. Furthermore, microbiome fluctuations or metabolic endotoxemia are proposed as possible disorder biomarkers. Based on the fact that gut microbiota dysbiosis reverts to a state of eubiosis in long-term patients with this condition, it may be hypothesized that disease progression begins with the loss of beneficial gut microorganisms, particularly short-chain fatty acid producers, leading to more widespread gastrointestinal phenotypes that are subsequently reflected in plasma metabolite levels. These alterations, specific of each individual, thereby result in metabolic and phenotypic shifts and in ME/CFS.
Natural killer (NK) cells demonstrate potent cytotoxic activities and the capacity to secrete cytokines. Their distinctive capability to trigger cell death, bypassing the need for major histocompatibility complex recognition, opens promising avenues for their use in clinical settings such as allogeneic transplantation and tumor immunotherapy. Although the ability of NK cells to kill hematological tumors has been widely recognized, their effectiveness in treating solid tumors is not as pronounced. The intricate interplay of NK cells with the tumor microenvironment, specifically in the context of solid malignancies, has been noted to attenuate the anti-cancer prowess of NK cells and foster the ability of malignant cells to elude immune surveillance. Successful NK cell-centered immunotherapy hinges on obtaining a substantial quantity of NK cells with potent tumor-killing capabilities. However, the current challenge lies in the limited ex vivo expansion of NK cells and the inefficiency of gene introduction methods. Induced pluripotent stem cells (iPSCs) are multipotent stem cells with relatively easier gene transfection capability and theoretically unlimited proliferation potential. NK cells derived from iPSCs circumvent the challenge of difficult genetic modification in NK cells, offering various potential strategies to counteract the immune suppression induced by the tumor microenvironment.
Different human diseases have been associated with specific blood groups. Numerous studies have promulgated their findings regarding the probable onset of various cancers based on the type of ABO blood group. However, the findings have been conflicting. This review primarily aims to summarize research findings from around the world to investigate the relationship between the risk of cancer occurrence and ABO blood group. Google Scholar, PubMed, Research4Life, and Web of Science were searched to identify relevant papers published before January 2023. Research papers related to common types of cancers were adequately and critically studied to determine the link between ABO blood groups and the risk of developing cancers. The results were ambiguous, as the findings were inconsistent regarding the relationship between ABO blood groups and cancer development. Therefore, more comprehensive research is needed to validate this relationship. This mini-systematic review emphasizes the need for additional thorough investigations to establish a clear correlation because of the inconsistent results.
Copper is an essential trace element in living organisms and is involved in a variety of biochemical processes, including cellular respiration, iron metabolism, and nerve function. In recent years, research has shown that copper is not only essential for fundamental physiological functions but also plays an important role in immune response and pathological states. In particular, copper death (cuproptosis), a recently discovered cell death pathway that is strongly associated with copper overload, is emerging as an appealing area of immune research. Excess copper can induce cell death as a result of copper ions directly binding to sulfide proteins in the tricarboxylic acid cycle. In-depth studies of copper metabolism and its related mechanisms will contribute to developing new diagnostic tools and therapeutic strategies and providing new ideas and approaches for tackling infections and other related diseases. This review summarizes the newest understanding of copper death and the latest advancements in disease diagnosis and treatment, providing a valuable reference for the follow-up research on tuberculosis-related vaccines and copper in immunity.
Brucellosis is a zoonotic disease caused by Brucella spp., affecting different body systems and leading to multiple complications. Although brucellosis is prevalent in several regions, including Saudi Arabia, limited research has focused on childhood brucellosis. This study aimed to characterize the features and outcomes of brucellosis in pediatric patients. We conducted a retrospective descriptive study involving children (<18 years) with confirmed brucellosis (diagnosed through culture, serology, or both) who received antibiotic therapy. Subjects were stratified into two groups based on age: younger (≤8 years) and older (>8 years). We assessed treatment outcomes, including clinical cure, mortality, and hospital length of stay. A total of 20 patients were included, with 52.3% in the younger group and 47.7% in the older group. The majority were male (65%), with a mean age of 8.9 years, and 45% required hospitalization. Out of all the patients, only 6 (30%) reported consuming dairy products. Serologically, the baseline median antibody titers for Brucella melitensis and Brucella abortus were 1:1280 and 1:640, respectively. In the younger group, half reported arthralgia and presented with fever. While white blood cell elevation was not significant, C-reactive protein, erythrocyte sedimentation rate, and liver enzymes were elevated at baseline. The administered regimen varied, but about half of the patients received at least three antibiotics. All patients experienced clinical cures, and there were no deaths. This study highlights the characteristics of pediatric brucellosis in a country where the disease is endemic and provides evidence of positive prognosis associated with appropriate antibiotic therapy.
Hyphaene thebaica honey, commonly known as doum honey (DH), is widely utilized in the Mediterranean region due to its putative health benefits. However, the precise mechanisms underpinning these benefits remain obscure. This study sought to assess the anti-infective, anti-inflammatory, and anticancer properties of DH, and analyze its polyphenolic composition. The antibacterial effects of DH were tested against a range of multidrug-resistant Gram-positive and Gram-negative bacterial strains. In addition, we investigated the anti-inflammatory, antioxidant, and anticancer activities of DH in the MDA-MB-231 human breast cancer cell line. The phenolic compounds in DH were evaluated using quantitative high-performance liquid chromatography (HPLC). The model used to assess the anti-inflammatory properties was lipopolysaccharide (LPS)-activated macrophages. HPLC analysis revealed nine phenolic compounds in DH: Gallic acid, caffeic acid, carvacrol, p-coumaric acid, ellagic acid, kaempferol, pinobanksin, pinocembrin, and galangin. The minimum inhibitory concentration (MIC) values for DH varied between 0.19% and 0.78% w/w for the three Gram-positive strains tested and between 0.024% and 0.39% w/w for the four Gram-negative strains tested. Among all the bacterial strains tested, Escherichia coli was found to be the most susceptible, with an MIC of 0.024% w/w. Upon treating LPS-activated THP-1-derived macrophages with DH, the levels of nitric oxide were significantly diminished. Moreover, DH displayed a modest but significant cytostatic effect on the MDA-MB-231 cells. The most noticeable cytostatic impacts were observed at concentrations of 4 mg/mL and 2 mg/mL, resulting in a decrease in cell viability by 25% and 20%, respectively, compared to untreated control cells. A significant decline in the migration rate of MDA-MB-231 cells was observed following DH treatment compared to control cells (P < 0.05). Our findings not only corroborate the well-established antibacterial properties of DH but also imply that its recognized anticancer advantages may be partially attributed to its antioxidant, anti-inflammatory, cytostatic, and antimigration effects.
Typhoid fever, caused by Salmonella Typhi, remains a significant global public health concern, with an estimated 11 - 20 million cases annually. Vaccines are critical to controlling typhoid fever. Widespread vaccination diminishes the emergence of antibiotic-resistant strains of S. Typhi. The economic benefits of vaccination are also substantial, as the costs of treating typhoid fever and its complications can be significant. Ty21a®, a killed whole-cell vaccine, and Vivotif®, a live-attenuated vaccine, have been available for decades but have relatively short durations of action and only provide partial protection. Vi polysaccharide-conjugate vaccines have improved the durability of protection, but there is still room for improvement. Typhax™, a novel alternative to traditional conjugate vaccines, utilizes Vi polysaccharide that is non-covalently entrapped in a poly-L-lysine and CRM197 protein matrix crosslinked by glutaraldehyde. When formulated with Advax-CpG™ adjuvant, Typhax demonstrated promising results in a range of animal models including mice, rabbits, and non-human primates in which it induces high and sustained serum anti-Vi immunoglobulin G and serum bactericidal activity, without any safety or reactogenicity issues. This novel vaccine approach offers the potential for a low-cost, more effective, and durable vaccine against typhoid fever, avoiding the need for frequent booster doses.
The CXC chemokine receptor 5 (CXCR5) is a member of the G protein-coupled receptor family that is highly expressed in B cells and a subset of T cells, such as T follicular helper cells. Various types of cancers, including non-small cell lung cancer, breast cancer, and prostate cancer, also express CXCR5. Therefore, antibodies that specifically bind to CXCR5 could be useful for clarification of the mechanisms of cancer progression. In this study, we aimed to develop high-affinity monoclonal antibodies targeting mouse CXCR5 (mCXCR5) for flow cytometry. The established anti-mCXCR5 mAb (Cx5Mab-3; rat IgG2b, kappa), demonstrated reactivity with mCXCR5-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/mCXCR5) in flow cytometry. Kinetic analyses using flow cytometry indicated that the dissociation constants (KD) of Cx5Mab-3 for CHO/mCXCR5 cell is 7.2 × 10−10 M. Furthermore, Cx5Mab-3 did not cross-react with other mouse CC, CXC, CX3C, and XC chemokine receptors. These results indicate that Cx5Mab-3 is useful for detecting mCXCR5 in flow cytometry with high affinity and specificity.