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Recent studies indicate a significant relationship between malnutrition, frailty, and pleural effusion (PE), highlighting the critical role of muscle mass in patient outcomes. This review investigates the association between sarcopenia—characterized by a decline in skeletal muscle mass and function—and PE, marked by fluid accumulation in the pleural space. The findings reveal that sarcopenia is prevalent in patients with PE and is linked to increased postoperative complications and mortality rates. In liver transplantation, esophagectomy, and lung cancer surgeries, sarcopenia exacerbates the risk of adverse outcomes. Notably, preoperative muscle mass assessment serves as a predictive tool for identifying patients at higher risk of complications. This review underscores the importance of early diagnosis and intervention for sarcopenia to improve clinical outcomes in PE patients. The therapeutic approach should include comprehensive nutritional evaluations and targeted muscle-strengthening interventions. By addressing sarcopenia, healthcare providers can significantly reduce PE-related complications, enhance patient recovery, and improve survival rates. This review provides a foundation for future research to develop effective strategies for the management and treatment of sarcopenia in the context of PEs, aiming to optimize patient care and quality of life.

ABSTRACT The pathogenesis of COVID-19 is associated with a hyperinflammatory immune response. Monocytes and macrophages play a central role in this hyperinflammatory response to SARS-CoV-2. NLRP3 inflammasome activation has been observed in monocytes of patients with COVID-19, but the mechanism and consequences of inflammasome activation require further investigation. In this study, we inoculated a macrophage-like THP-1 cell line, primary differentiated human nasal epithelial cell (hNEC) cultures, and primary monocytes with SARS-CoV-2. We found that the activation of the NLRP3 inflammasome in macrophages does not rely on viral replication, receptor-mediated entry, or actin-dependent entry. SARS-CoV-2 productively infected hNEC cultures without triggering the production of inflammasome cytokines IL-18 and IL-1β. Importantly, these cytokines did not inhibit viral replication in hNEC cultures. SARS-CoV-2 inoculation of primary monocytes led to inflammasome activation and induced a macrophage phenotype in these cells. Monocytic cells from bronchoalveolar lavage (BAL) fluid, but not from peripheral blood, of patients with COVID-19, showed evidence of inflammasome activation, expressed the proinflammatory marker CD11b, and displayed oxidative burst. These findings highlight the central role of activated macrophages, as a result of direct viral sensing, in COVID-19 and support the inhibition of IL-1β and IL-18 as potential therapeutic strategies to reduce immunopathology without increasing viral replication.IMPORTANCEInflammasome activation is associated with severe COVID-19. The impact of inflammasome activation on viral replication and mechanistic details of this activation are not clarified. This study advances our understanding of the role of inflammasome activation in macrophages by identifying TLR2, NLRP3, ASC, and caspase-1 as dependent factors in this activation. Further, it highlights that SARS-CoV-2 inflammasome activation is not a feature of nasal epithelial cells but rather activation of bystander macrophages in the airway. Finally, we demonstrate that two pro inflammatory cytokines produced by inflammasome activation, IL-18 and IL-1β, do not restrict viral replication and are potential targets to ameliorate pathological inflammation in severe COVID-19.

Naïve CD8+ T cells can differentiate into effector (Teff), memory (Tmem) or exhausted (Tex) T cells. These developmental pathways are associated with distinct transcriptional and epigenetic changes that endow cells with different functional capacities and therefore therapeutic potential. The molecular circuitry underlying these developmental trajectories and the extent of heterogeneity within Teff, Tmem and Tex populations remain poorly understood. Here, we used the lymphocytic choriomeningitis virus model of acute-resolving and chronic infection to address these gaps by applying longitudinal single-cell RNA-sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analyses. These analyses uncovered new subsets, including a subpopulation of Tex cells expressing natural killer cell-associated genes that is dependent on the transcription factor Zeb2, as well as multiple distinct TCF-1+ stem/progenitor-like subsets in acute and chronic infection. These data also revealed insights into the reshaping of Tex subsets following programmed death 1 (PD-1) pathway blockade and identified a key role for the cell stress regulator, Btg1, in establishing the Tex population. Finally, these results highlighted how the same biological circuits such as cytotoxicity or stem/progenitor pathways can be used by CD8+ T cell subsets with highly divergent underlying chromatin landscapes generated during different infections.

Pleural mesothelioma (PM) is a tumor related to adverse prognosis. The PM WHO classification has mainly identified three major subtypes of PM which are epithelioid, biphasic, and sarcomatoid. Sarcopenia is a medical issue related to a reduction in muscle mass and strength. It represents a major health issue globally because it is related to adverse effects such as hospitalization, increased length of stay, disability, increased morbidity and mortality and augmented health care expenditures. In this literature review, we attempted to examine the upcoming association between sarcopenia and PM. As recorded by the current literature, muscle loss in PM subjects was related to poorer survival and lower levels of activity. Subjects with PM had increased rates of pre-sarcopenia and malnutrition, while pre-sarcopenia was related to worse activity levels, and malnutrition was related to worse quality of life (QoL). Both tumor volume and sarcopenia were related to long-term mortality in surgically treated PM subjects, while sarcopenia was present both pre-operatively and post-operatively in these subjects. In addition, post-operative sarcopenic subjects showed a decreased 3-year overall survival (OS) in comparison with those who did not have sarcopenia, while pre-operative sarcopenia was importantly related to an increased rate of post-operative adverse outcomes. More studies are needed to validate these claims.

Background: Loop diuretics (LDs) are used to treat various health conditions including heart failure (HF), liver cirrhosis, and chronic kidney disease (CKD). Sarcopenia is a skeletal muscle health issue related to the depletion and decrease of muscle mass and strength, leading to adverse outcomes including frailty syndrome, functional decline, falls, hospitalizations, augmented length of hospital stay, and increased morbidity and mortality. Methods: This study investigated the probable association between LD use and sarcopenia via conducting a non-systematic review of the existing literature. Results: In subjects with non-dialysis-dependent chronic kidney disease (NDD-CKD), an augmented risk of sarcopenia is significantly associated with LD use. Interestingly, in patients with HF treated with LDs, thigh and arm circumferences were significantly small, which is indicative of skeletal muscle wasting. Additionally, in anorexic subjects who are more likely to be on diuretic medication, suffering also from cachexia, a higher prevalence of sarcopenia was demonstrated. In cirrhotic subjects, the treatment dosage of LDs was inversely correlated with the skeletal muscle area per year (ΔSMA). Nevertheless, in subjects with liver cirrhosis treated with LDs, who were divided into those with and those without muscle cramps, the presence of sarcopenia was similar. Conclusions: Further investigation is imperative to validate potential interplay between LDs and sarcopenia.

BackgroundPrevious studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN).MethodsBALB/c mice aged 6–8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α. In a small-scale (n = 3/group) experiment, mice immunized IM with electroporation were followed up for serum antibody concentrations over a period of 1 year and for bronchoalveolar antibody levels at the termination of the study. Following IN immunization with unencapsulated plasmid DNA (n = 6/group), mice were evaluated at 11 weeks for serum antibody concentrations, quantities of T cells in the lungs, and IFN-γ- and TNF-α-expressing antigen-specific T cells in the lungs and spleen.ResultsAt 12 months postprimary vaccination, recipients of the IM vaccine incorporating MIP-3α had significantly, approximately threefold, higher serum antibody concentrations than recipients of the vaccine not incorporating MIP-3α. The area-under-the-curve analyses of the 12-month observation interval demonstrated significantly greater antibody concentrations over time in recipients of the MIP-3α vaccine formulation. At 12 months postprimary immunization, only recipients of the fusion vaccine had concentrations of serum-neutralizing activity deemed to be effective. After intranasal immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs significantly above those of PBS controls. Low levels of serum antibody responses were obtained following IN immunization.ConclusionAlthough requiring separate IM and IN immunizations for optimal immunization, incorporating MIP-3α in a SARS-CoV-2 vaccine construct demonstrated the potential of a stable and easily produced vaccine formulation to provide the extended antibody and T-cell responses that may be required for protection in the setting of emerging SARS-CoV-2 variants. Without electroporation, simple, uncoated plasmid DNA incorporating MIP-3α administered intranasally elicited lung T-cell responses.

A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact that cancer metabolism affects not just cancer signaling, which is essential for maintaining carcinogenesis and survival, but also the expression of immune cells and immune-related factors such as lactate, PGE2, arginine, IDO, which regulate the antitumor immune signaling mechanism. In reality, this energetic interaction between the immune system and the tumor results in metabolic competition in the tumor ecosystem, limiting the amount of nutrients available and causing microenvironmental acidosis, which impairs the ability of immune cells to operate. More intriguingly, different types of immune cells use metabolic reprogramming to keep the body and self in a state of homeostasis. The process of immune cell proliferation, differentiation, and performance of effector functions, which is crucial to the immune response, are currently being linked to metabolic reprogramming. Here, we cover the regulation of the antitumor immune response by metabolic reprogramming in cancer cells and immune cells as well as potential strategies for metabolic pathway targeting in the context of anticancer immunotherapy. We also discuss prospective immunotherapy-metabolic intervention combinations that might be utilized to maximize the effectiveness of current immunotherapy regimes.

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches.

Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines’ clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future.