Compromised Immune Response Research Articles

Understanding Diabetic Wounds: A Review of Mechanisms, Pathophysiology, and Multimodal Management Strategies

Introduction: Diabetic wounds are a prevalent and impairing consequence of diabetes mellitus that significantly impacts people's lives and global healthcare systems. Because of disturbances in the wound-healing cascade, these intricate, persistent wounds frequently refuse to heal. Focusing on diabetic wound formation, this study seeks to clarify the complex mechanisms and pathophysiology involved while offering a thorough overview of modern multimodal therapy techniques. The etiology of diabetic wounds entails a complex interplay between tissue destruction caused by hyperglycemia, neuropathy, ischemia, and compromised immune response. Extended inflammation, abnormal protease activity, and low oxygen levels in the tissue exacerbate the healing process. Comprehending these pathogenic mechanisms is essential for formulating efficacious therapeutic strategies. Methodology: A thorough evaluation of the literature was done. Databases like SciFinder, ScienceDirect, PubMed, Google, Google Scholar, and the Egyptian Knowledge Bank were used to find pertinent publications. More than 200 articles and databases were studied to constitute this paper. The accuracy of the retrieved data was carefully reviewed and cross-checked. The current review aims to define wounds, various methods of classification, and various advancements for wound management as mentioned in scheme 1. Several multidisciplinary strategies, including debridement, unloading, antimicrobial stewardship, and innovative therapeutics, are currently needed to manage diabetic wounds. Debridement—the excision of non-viable tissue—is necessary to create an environment that is conducive to recovery. Biomechanical interventions and offloading help to prevent additional tissue damage caused by repetitive stress. Antimicrobial treatments fight infections, which are a common diabetic wound consequence. Promising supplementary treatments are provided by developments in cellular and tissue-based products, ozone therapy growth factors, bioengineered skin substitutes, and hyperbaric oxygen therapy. Result: After applying article selection criteria and reviewing the quality of the methodology a total of 200 articles were selected to be included in the review. In this review, intricate interactions between peripheral neuropathy, vascular insufficiency, and hyperglycemia in the pathophysiology of diabetic wounds are explained. The efficacy of multimodal therapies is discussed in detail. Discussion: A thorough comprehension of the complex mechanisms that underlie diabetic wounds is essential for efficient therapy. This review emphasizes how important multimodal approaches are to treating the complex pathophysiology of these wounds. Clinicians can greatly enhance the prognosis of patients with diabetic foot ulcers by addressing vascular insufficiency, neuropathy, infection, and poor healing. Conclusion: Timely wound resolution remains a key difficulty despite the implementation of multimodal methods. To customize therapies, personalized medicine strategies utilizing genetic and proteomic biomarkers must be the main focus of future research. Furthermore, cutting-edge biotechnologies with the potential to transform diabetic wound treatment include optogenetics and nanomedicine.

Methicillin-Resistant Staphylococcus aureus Secondary Infection as a Comorbid in Crusted Scabies Patient

Introduction: Crusted scabies (CS) is characterized by uncontrolled proliferation of mites up to thousands. Complications include glomerulonephritis, rheumatic fever, and secondary infection which can cause bacteremia and sepsis. This case report describes a case of CS that was hospitalized with secondary complications of MRSA infection. Case Presentation: A 44-year-old woman complained of thick scales and itching all over her body for 6 months. Complaints begin with reddish bumps between the fingers, toes, body, genitals, and scalp, accompanied by itching, especially at night. The patient took self-purchased corticosteroids for this complaint for 6 months. Dermatology status all over the body showed erythematous papules plaques with greenish-yellow scales, blackish crusts, hyperkeratosis, and excoriation, also erythematous base erosions and blackish crusts in the right thoracic region. Ectoparasite scrapping examination showed large amounts of Sarcoptes scabiei, eggs, and scybala, so the patient was diagnosed with Crusted scabies. A wound culture and nasal swab showed MRSA. The patient died of septic shock on day 12 of treatment. Discussion: Crusted scabies is a highly contagious form of scabies, characterized by thickening of the skin layer and crusts. Long-term corticosteroid consumption in this case caused a compromised immune response so that the number of mites multiplied rapidly and increased the risk of MRSA infection. MRSA mortality rates range from 5-60%. Conclusion: Ignored cases of scabies can develop into crusted scabies which have a high risk of secondary infection, such as MRSA which can cause serious morbidity and even mortality.

The Interplay between COVID-19 and Diabetes: Understanding Hyperglycemia, Complications, and Management Challenges in Diabetic Patients

The COVID-19 pandemic has significantly impacted individuals with diabetes, revealing a complex interplay between the virus and pre-existing hyperglycemia. This review explores how COVID-19 exacerbates hyperglycemia in diabetic patients, primarily through mechanisms such as stress response, cytokine storms, and increased insulin resistance. Diabetic individuals are particularly susceptible to severe COVID-19 outcomes, including heightened mortality rates, due to compromised immune responses and coexisting conditions like cardiovascular and renal complications. The review also addresses the unique challenges of managing diabetes during COVID-19, including the need for adjustments in insulin therapy and the impact of COVID-19 treatments, such as corticosteroids, on glucose control. Additionally, it highlights the potential long-term effects of COVID-19 on diabetic patients, including the onset of new diabetes and persistent metabolic issues. The review emphasizes the importance of glycemic control, vaccination, and holistic care approaches to mitigate the severity of COVID-19 in diabetic patients. Furthermore, it examines the psychological and socioeconomic impacts of the pandemic on this vulnerable population. As ongoing research continues to investigate the interaction between COVID-19 and diabetes, this review provides a comprehensive understanding of the challenges and future directions in managing diabetic patients during and after the pandemic. Keywords: COVID-19, Diabetes, Hyperglycemia, Complications, Management Challenges, Diabetic Patients

Favourable humoral but reduced cellular immune response to COVID-19 mRNA BNT162b2 vaccine in patients with childhood-onset systemic lupus erythematosus

ObjectiveTo evaluate both humoral and cellular immune responses to the COVID-19 messenger RNA (mRNA; BNT162b2) vaccine in patients with childhood-onset SLE (cSLE) compared with healthy controls and patient controls (kidney...

A Living Microecological Hydrogel with Microbiota Remodeling and Immune Reinstatement for Diabetic Wound Healing.

Dysregulated skin microbiota and compromised immune responses are the major etiological factors for non-healing diabetic wounds. Current antibacterial strategies fail to orchestrate immune responses and indiscriminately eradicate bacteria at the wound site, exacerbating the imbalance of microbiota. Drawing inspiration from the beneficial impacts that probiotics possess on microbiota, a living microecological hydrogel containing Lactobacillus plantarum and fructooligosaccharide (LP/FOS@Gel) is formulated to remodel dysregulated skin microbiota and reinstate compromised immune responses, cultivating a conducive environment for optimal wound healing. LP/FOS@Gel acts as an "evocator," skillfully integrating the skin microecology, promoting the proliferation of Lactobacillus, Ralstonia, Muribaculum, Bacillus, and Allobaculum, while eradicating colonized pathogenic bacteria. Concurrently, LP/FOS@Gel continuously generates lactic acid to elicit a reparative macrophage response and impede the activation of the nuclear factor kappa-B pathway, effectively alleviating inflammation. As an intelligent microecological system, LP/FOS@Gel reinstates the skin's sovereignty during the healing process and effectively orchestrates the harmonious dialogue between the host immune system and microorganisms, thereby fostering the healing of diabetic infectious wounds. These remarkable attributes render LP/FOS@Gel highly advantageous for pragmatic clinical applications.

Exploring the associations between gut microbiota composition and SARS-CoV-2 inactivated vaccine response in mice with type 2 diabetes mellitus.

Over 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.

Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China

ObjectiveThe current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred.MethodA cross‐sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared.ResultPatients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO.ConclusionThis present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.

The association of inflammatory markers with frailty and in-hospital mortality in older COVID-19 patients

IntroductionDuring the COVID19 pandemic, older patients hospitalized for COVID-19 exhibited an increased mortality risk compared to younger patients. While ageing is associated with compromised immune responses and frailty, their contributions and interplay remain understudied. This study investigated the association between inflammatory markers and mortality and potential modification by frailty among older patients hospitalized for COVID-19. MethodsData were from three multicenter Dutch cohorts (COVID-OLD, CliniCo, Covid-Predict). Patients were 70 years or older, hospitalized for COVID-19and categorized into three frailty groups: fit (Clinical frailty score (CFS) 1–3), pre-frail (CFS 4–5), and frail (CFS 6–9). Immunological markers (lymphocyte count, neutrophil count, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammation index (SII)) were measured at baseline. Associations with in hospital mortality were examined using logistic regression. ResultsA total of 1697 patients were included from COVID-OLD, 656 from Covid-Predict, and 574 from CliniCo. The median age was 79, 77, and 78 years for each cohort. Hospital mortality rates were 33 %, 27 % and 39 % in the three cohorts, respectively. A lower CRP was associated with a higher frailty score in all three cohorts (all p < 0.01). Lymphocyte count, neutrophil count, NLR, PLR, or SII, were similar across frailty groups. Higher CRP levels were associated with increased in-hospital mortality risk across all frailty groups, across all cohorts (OR (95 % CI), 2.88 (2.20–3.78), 3.15 (1.95–5.16), and 3.28 (1.87–5.92)), and frailty did not modify the association between inflammatory markers and in-hospital mortality (all p-interaction>0.05). ConclusionWhile frailty is a significant factor in determining overall outcomes in older patients, our study suggests that the elevated risk of mortality in older patients with frailty compared to fit patients is likely not explained by difference in inflammatory responses.

Alterations of plasma metabolomes and their correlations with immunogenicity in maintenance hemodialysis patients receiving different COVID-19 vaccine regimens.

Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID-19 vaccine than the general population. The metabolomic factors influencing COVID-19 vaccine response in MHD patients remain elusive. A cross-sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV-SV), homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost (SV-AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ-AZ and SV-SV, followed by SV-AZ versus SV-SV, and AZ-AZ versus SV-AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID-19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients.

Integrated Transcriptomic Analysis Reveals Reciprocal Interactions between SARS-CoV-2 Infection and Multi-Organ Dysfunction, Especially the Correlation of Renal Failure and COVID-19.

The COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, has resulted in extensive health challenges globally. While SARS-CoV-2 primarily targets the respiratory system, clinical studies have revealed that it could also affect multiple organs, including the heart, kidneys, liver, and brain, leading to severe complications. To unravel the intricate molecular interactions between the virus and host tissues, we performed an integrated transcriptomic analysis to investigate the effects of SARS-CoV-2 on various organs, with a particular focus on the relationship between renal failure and COVID-19. A comparative analysis showed that SARS-CoV-2 triggers a systemic immune response in the brain, heart, and kidney tissues, characterized by significant upregulation of cytokine and chemokine secretion, along with enhanced migration of lymphocytes and leukocytes. A weighted gene co-expression network analysis demonstrated that SARS-CoV-2 could also induce tissue-specific transcriptional profiling. More importantly, single-cell sequencing revealed that COVID-19 patients with renal failure exhibited lower metabolic activity in lung epithelial and B cells, with reduced ligand-receptor interactions, especially CD226 and ICAM, suggesting a compromised immune response. A trajectory analysis revealed that COVID-19 patients with renal failure exhibited less mature alveolar type 1 cells. Furthermore, these patients showed potential fibrosis in the hearts, liver, and lung increased extracellular matrix remodeling activities. However, there was no significant metabolic dysregulation in the liver of COVID-19 patients with renal failure. Candidate drugs prediction by Drug Signatures database and LINCS L1000 Antibody Perturbations Database underscored the importance of considering multi-organ effects in COVID-19 management and highlight potential therapeutic strategies, including targeting viral entry and replication, controlling tissue fibrosis, and alleviating inflammation.

Deciphering the prognostic role of endoplasmic reticulum stress in lung adenocarcinoma: integrating prognostic prediction and immunotherapy strategies

Endoplasmic reticulum stress (ERS) is a critical factor influencing lung adenocarcinoma (LUAD) progression and patient outcomes. In this study, we analyzed gene expression data from LUAD samples sourced from The Cancer Genomic Atlas and Gene Expression Omnibus databases. Utilizing advanced statistical methods including LASSO and Cox regression, we developed a ERS-associated signature (ERAS) based on ten ERS-related genes. This model stratified patients into high- and low-risk groups, with the high-risk group exhibiting decreased survival rates, elevated tumor mutational burden, and heightened chemotherapy sensitivity. Additionally, we observed lower immune and ESTIMATE scores in the high-ERAS group, indicating a potentially compromised immune response. Experimental validation through quantitative real-time polymerase chain reaction confirmed the utility of our model. Furthermore, we constructed a nomogram to predict 1-, 3-, and 5-year survival rates, providing clinicians with a valuable tool for personalized patient management. In conclusion, our study demonstrates the efficacy of the ERAS in identifying high-ERAS LUAD patients, offering promising implications for improved prognostication and treatment strategies.

Evaluation of therapeutic outcomes in emphysematous pyelonephritis: a single-center experience at Siriraj Hospital

Objective: Emphysematous pyelonephritis (EPN) is an acute, severe, necrotizing parenchymal and perirenal infection associated with high morbidity and mortality. The radiographic classifications, which determine the treatment strategies, however, remain controversial. Our study aimed to evaluate and compare the clinical parameters related to nephrectomy and the treatment outcomes in current practices. Materials and Methods: We retrospectively reviewed the data from 21 EPN patients who had been diagnosed using computed tomography (CT) scans, who were admitted to Siriraj Hospital from January 2009 to December 2019. The clinical manifestations, imaging results, laboratory findings, treatment methods, and overall outcomes of each patient were reviewed and analyzed. Huang–Tseng’s and Wan’s classifications were used to classify the images obtained from the CT scans. Results: Among the 21 patients with EPN, all had at least one comorbidity associated with a compromised immune response. Common manifestations included fever (74%) and initial laboratory findings showed hyperglycemia (66%), acute kidney injury (72%), and metabolic acidosis (76%). Inotropes were used in 13 patients for hemodynamic support. Eleven patients were treated with a non-nephrectomy approach, while 10 patients underwent nephrectomy. No statistical difference in treatment outcomes was observed between groups in both classification systems. Overall survival was 100% with a minimum one-year follow-up. Conclusion: Our study demonstrated that the current treatment approach has resulted in a zero mortality rate of EPN most probably due to advancements in antibiotics, surgical techniques, and postoperative intensive care over the years. However, refining treatment strategies, considering radiographic criteria, clinical parameters, and initial treatment response, is essential in future studies to further decrease disease morbidity.

Current trends and advances in antiviral therapy for chronic hepatitis B

Abstract Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.

Exploring the Link between Varicella-Zoster Virus, Autoimmune Diseases, and the Role of Recombinant Zoster Vaccine.

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases.

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection.

The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen.

Thirty days of double-strain probiotic supplementation increases monocyte phagocytosis in marathon runners.

Marathon runners, subjected to intense training regimens and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: placebo (n 13) and probiotic (PRO) (n 14). Over 30 d, both groups received supplements - placebo sachets containing maltodextrin (5 g/d) and PRO sachets containing 1 × 1010 colony-forming unit Lactobacillus acidophilus and 1 × 1010 colony-forming unit Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels and monocyte immunophenotyping, were conducted at four different intervals: baseline (start of supplementation/30 d pre-marathon), 24 h-before (1 d pre-marathon), 1 h-after (1 h post-marathon) and 5 d-after (5 d post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after 30 d of supplementation. Upon lipopolysaccharide stimulation, both PRO and placebo groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5 d-after, while IL-1-β, IL-8, IL-10, IL-15 and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning.

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.

Season, size, and sex: factors influencing monogenean prevalence and intensity on Gambusia affinis in New Zealand

A number of studies have been conducted on monogenean seasonality, though primarily in continental regions with wide annual temperatures ranges. We investigated seasonal changes in the prevalence and intensity of Salsuginus seculus infesting sexually dimorphic western mosquitofish (Gambusia affinis) in New Zealand. This represents the first examination of seasonality for this species globally, and the first seasonal assessment of any monogenean population in New Zealand, a temperate country with a mild oceanic climate. Prevalence and intensity of S. seculus with respect to fish size and sex was also examined. Prevalence of S. seculus changed temporally, peaking in summer, and was strongly positively correlated with algal concentrations. This relationship may be associated with increasing food levels, leading to an increase in fish courting and mating, resulting in high numbers and close physical associations of G. affinis individuals, facilitating transmission of the monogeneans. Thus, biotic factors may be important in determining temporal changes in S. seculus prevalence in New Zealand. Female G. affinis had a significantly higher prevalence and mean intensity of S. seculus than males. Longer fish had a higher mean intensity and prevalence of S. seculus. Female G. affinis likely host disproportionately more monogeneans as they are larger than males. Alternatively, females may have a compromised immune response during reproductive periods. Overall, seasonal change was observed in S. seculus prevalence and intensity under New Zealand’s mild climatic conditions, and the larger female G. affinis in this dimorphic species supported a greater prevalence and intensity of infestation than males.

Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.