Global Health Challenge Research Articles

Advances in clinical research on pharmacological management of chemotherapy-induced constipation in gastrointestinal tumor: A perspective.

Gastrointestinal tumors, including those of the stomach, colon, rectum, and esophagus, present significant global health challenges. Chemotherapy, essential for treating these cancers, often causes constipation, adversely affecting patients' quality of life. This study examines the mechanisms behind chemotherapy-induced constipation, such as the direct impact of chemotherapeutic drugs on intestinal function, reduced fluid intake, decreased physical activity, opioid use, and psychological stress. While traditional treatments like stimulant and osmotic laxatives are commonly used, emerging therapies such as 5-HT4 receptor agonists and probiotics show promise. Traditional Chinese medicine offers additional strategies with herbal remedies and dietary adjustments. Future research should prioritize precision medicine, combining pharmacological and non-pharmacological approaches, and developing innovative therapeutics utilizing biologics and nanotechnology. Ongoing research is crucial for improving chemotherapy-induced constipation management, aiming to enhance treatment outcomes and the quality of life for chemotherapy patients with gastrointestinal tumors.

Insights into the Rising Threat of Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa Epidemic Infections in Eastern Europe: A Systematic Literature Review.

Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-β-lactamase-producing CRPA strains. This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed.

Insights into Metabolic Reprogramming in Tumor Evolution and Therapy.

Background: Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. Objectives: This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. Methods: It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes. Results: This review emphasizes the significance of targeting these metabolic pathways for therapeutic intervention, outlining the potential to disrupt cancer's energy supply and signaling mechanisms. It calls for an interdisciplinary research approach to fully understand and exploit the intricacies of cancer metabolism, pointing toward metabolic reprogramming as a promising frontier for developing more effective cancer treatments. Conclusion: By equating cancer's metabolic complexity with the enigmatic nature of dark matter and energy, this review underscores the critical need for innovative strategies in oncology, highlighting the importance of unveiling and targeting the "dark energy" within cancer cells to revolutionize future therapy and research.

Identifying Candida auris transmission in a hospital outbreak investigation using whole-genome sequencing and SNP phylogenetic analysis.

Candida auris poses a global public health challenge, causing multiple outbreaks within healthcare facilities. Despite advancements in strain typing for various infectious diseases, a consensus on the genetic relatedness threshold for identifying C. auris transmission in local hospital outbreaks remains elusive. We investigated genetic variations within our local isolate collection using whole-genome-based single nucleotide polymorphism (SNP) phylogenetic analysis. A total of 74 C. auris isolates were subjected to whole-genome sequencing (WGS) and SNP phylogenetic analysis via the QIAGEN CLC Genomics Workbench. Isolates included known related strains from the same patient, strains from different hospitals, strains from our hospital patients with no epidemiological link, and 19 patient isolates from a recent C. auris outbreak. All but three isolates were identified to be Clade IV. By examining the genetic diversities of C. auris within patients and between patients, we identified a SNP variation range of 0-13 for identifying related isolates. During an outbreak investigation, utilizing this range, maximum likelihood phylogenetic analysis revealed two distinct clusters that aligned with the epidemiological links. Determining a SNP variation range to delineate genetic relatedness among isolates is crucial for the application of WGS and SNP phylogenetic analysis in identifying C. auris transmission during hospital outbreak investigations. The use of WGS SNP phylogenetic analysis via the CLC Genomics Workbench has emerged as a valuable method for typing C. auris in clinical microbiology laboratories.

Recent advances in HPV biotechnology: Understanding host-virus interactions and cancer progression-a review

Cervical cancer ranks as the fourth most common cancer among women globally, posing a significant mortality risk. Persistent infection with high-risk human papillomavirus (HPV) is the primary instigator of cervical cancer development, often alongside co-infection with other viruses, precipitating various malignancies. This study aimed to explore recent biotechnological advances in understanding HPV infection dynamics, host interactions, and its role in oncogenesis. The gathered data shed light on HPV biology, host-virus interplay, viral co-infections, and cellular transformations leading to HPV-associated cancers. Recent years have seen the introduction of diverse vaccination strategies, including live attenuated, subunit, and DNA-based vaccines, complemented by innovative nanotechnology and plant-based products. Despite rich data addressing research inquiries, urgent calls echo for the implementation of contemporary screening and therapeutic modalities at clinical levels. Moreover, extensive public awareness campaigns are imperative to alleviate the burden of HPV-related diseases, emphasizing the necessity for proactive intervention strategies in combating this global health challenge.

Small-molecule natural product sophoricoside reduces peripheral neuropathic pain via directly blocking of NaV1.6 in dorsal root ganglion nociceptive neurons.

Peripheral neuropathic pain poses a significant global health challenge. Current drugs for peripheral neuropathic pain often fall short in efficacy or come with severe side effects, emphasizing the critical need for the development of highly effective and well-tolerated alternatives. Sophoricoside (SOP) is a nature product-derived isoflavone that possesses various pharmacological effects on inflammatory and neuropathy diseases. Here, in this study, analgesic effect was investigated by intrathecally administration of SOP/vehicle to spared nerve injury (SNI) or paclitaxel-induced peripheral neuropathic pain (PINP) rodent models, and mechanical allodynia was measured in Von Frey tests. Ipsilateral L4-L6 dorsal root ganglia (DRG) were used for protein expression. In silico molecular docking analysis was applied for assessing compound-target binding affinity. Primary cultured DRG neurons were utilized to investigate SOP's effect on veratridine-triggered nociceptor activities and its selective inhibition of voltage-gated sodium channels subtype 1.6 (NaV1.6). The results showed SOP treatment alleviated mechanical allodynia in SNI and PINP rodent models (paw withdrawal threshold after 1 h of injection: SNI-vehicle: 1.385 ± 0.338 g; SNI-SOP: 9.963 ± 2.029 g, P < 0.001; PINP-vehicle: 5.040 ± 0.985 g; PINP-SOP: 8.287 ± 3.812 g, P = 0.004). SOP presented effects on both inhibiting veratridine-triggered nociceptor activities (oscillatory population: vehicle: 39.9 ± 7.3%; SOP: 30.7 ± 9.8%, P = 0.021) and selectively blocking NaV1.6 in DRG sensory neurons. Molecular docking analysis indicated direct binding between SOP and NaV1.6, leading to its endocytosis in DRG Sensory Neurons. In conclusion, SOP alleviated nociceptive allodynia induced by peripheral nerve injury via selectively blocking of NaV1.6 in DRG nociceptive neurons. we highlight its potential as an analgesic and elucidate its mechanism involving NaV1.6 endocytosis. This research opens avenues for exploring the analgesic effects of SOP and its potential impact on neuropathic pain therapy.

Improved Therapeutic Efficacy: Liposome-Coated Mesoporous Silica Nanoparticles Delivering Thymoquinone to MCF-7 Cells.

Breast cancer remains a significant global health challenge, with thymoquinone showing promise as a therapeutic agent, but hindered by poor solubility. This study aimed to enhance TQ delivery to MCF-7 breast cancer cells using mesitylene- mesoporous silica nanoparticles coated with liposomes, designed for controlled drug release. Nanoparticles were synthesized using the sol-gel method and coated with phosphatidylserine- cholesterol liposomes. Different nanocharacterization techniques and in vitro assays were employed to assess the drug release kinetics, cellular uptake, cytotoxicity, and apoptosis. The nanoparticles exhibited favorable properties, including a large pore size of 3.6 nm, a surface area of 248.96 m2/g, and a hydrodynamic size of 171.571 ± 8.342 nm with a polydispersity index of 0.182 ± 0.017, indicating uniformity and stability. The successful lipid bilayer coating was confirmed by a zeta potential shift from +6.25 mV to -5.65 mV. The coated nanoparticles demonstrated a slow and sustained drug release profile, with cellular uptake of FITC-formulated nanoparticles being approximately 5-fold higher than free FITC (P < 0.0001). Cytotoxicity assays revealed a significant reduction in cell viability (P < 0.0001), reaching an IC50 value of 25 μM at 48 hours. Apoptosis rates were significantly higher in cells treated with the formulated TQ compared to the free drug and control at both 24 and 48 hours (P < 0.0001). This nanoformulation significantly enhanced TQ delivery, offering a promising strategy for targeted breast cancer therapy. Further preclinical studies are recommended to advance this approach in cancer treatment.

Change in the prevalence of anemia in children aged 6-59 months using the new World Health Organization 2024 criteria.

The World Health Organization (WHO) has published new hemoglobin cutoff points for defining anemia and its measurement. This change could impact the prevalence of anemia, particularly in countries with populations living in high-altitude areas. This study estimates the national prevalences of anemia in children aged 6-59 months using Centers for Disease Control and Prevention (CDC) 1989 and WHO 2024 criteria. Data from 406,106 children in 48 countries (45 Demographic and Health Surveys [DHS Program] and 3 Andean [Ecuador, Bolivia, and Peru]) were analyzed. The pooled prevalence of anemia was 61.4% according to the WHO 2024 criteria. Three countries showed changes in anemia prevalence, with shifts of 10 or more percentage points (Uganda, Rwanda, and Jordan). Across all the studied countries, the prevalence of anemia was higher at greater altitudes, rural areas, and children from households of low wealth quintiles, regardless of the criteria used. Moreover, changes in anemia prevalence were identified when stratified by altitude of residence, showing differences in the levels of public health significance across various political-administrative regions in Andean countries. Overall, these findings provide valuable insights into the epidemiology of anemia and highlight the need for continued surveillance and targeted interventions to effectively address this global health challenge.

Artificial intelligence-driven predictive framework for early detection of still birth

Predictive modeling is becoming increasingly popular in the context of early disease detection. The use of machine learning approaches for predictive modeling can help early detection of diseases thereby enabling medical experts to appropriate medical treatments. Stillbirth prediction is a similar domain where artificial intelligence-based predictive modeling can alleviate this significant global health challenge. Despite advancements in prenatal care, the prevention of stillbirths remains a complex issue requiring further research and interventions. The cardiotocography (CTG) dataset is used in this research work from the UCI machine learning (ML) repository to investigate the efficiency of the proposed approach regarding stillbirth prediction. This research work adopts the Tabular Prior Data Fitted Network (TabPFN) model which was originally designed to solve small tabular classification. TabPFN is used to predict the still or live birth during pregnancy with 97.91% accuracy. To address this life-saving problem with more accurate results and in-depth analysis of ML models, this research work makes use of 13 renowned ML models for performance comparison with the proposed model. The proposed model is evaluated using precision, recall, F-score, Mathews Correlation Coefficient (MCC), and the area under the curve evaluation parameters and the results are 97.87%, 98.26%, 98.05%, 96.42%, and 98.88%, respectively. The results of the proposed model are further evaluated using k-fold cross-validation and its performance comparison with other state-of-the-art studies indicating the superior performance of TabPFN model.

Macrophage activation syndrome in Sepsis: from pathogenesis to clinical management.

Sepsis represents a significant global health and hygiene challenge. Excessive activation of macrophages in sepsis can result in certain patients displaying characteristics akin to those observed in Macrophage Activation Syndrome (MAS). MAS represents a grave immune system disorder characterized by persistent and severe inflammation within the body. In the context of sepsis, MAS presents atypically, leading some researchers to refer to it as Macrophage Activation-Like Syndrome (MALS). However, there are currently no effective treatment measures for this situation. The purpose of this article is to explore potential treatment methods for sepsis-associated MALS. The objective of this review is to synthesize the specific pathophysiological mechanisms and treatment strategies of MAS to investigate potential therapeutic approaches for sepsis-associated MALS. We searched major databases (including PubMed, Web of Science, and Google Scholar etc.) for literature encompassing macrophage activation syndrome and sepsis up to Mar 2024 and combined with studies found in the reference lists of the included studies. We have synthesized the underlying pathophysiological mechanism of MALS in sepsis, and then summarized the diagnostic criteria and the effects of various treatment modalities utilized in patients with MAS or MALS. In both scenarios, heterogeneous treatment responses resulting from identical treatment approaches were observed. The determination of whether the patient is genuinely experiencing MALS significantly impacts the ultimate outcomes of therapeutic efficacy. In order to tackle this concern, additional clinical trials and research endeavors are imperative.

Human Schistosomiasis due to Schistosoma bovis in Nigeria.

Schistosomiasis is a global public health challenge, especially in sub-Saharan Africa, where Nigeria has the highest burden of disease. Schistosoma hybrids have been discovered in various countries, including Nigeria, where livestock and human beings share common water resources. This study, carried out in three communities, two of which are endemic for urinary schistosomiasis, aimed to identify the urinary schistosomiasis causative agent by using a species-specific molecular technique and their evolutionary relationship. Polymerase chain reaction using primers specific for a partial DNA sequence of the mitochondrial cox1 gene of Schistosoma haematobium was carried out on pooled urine sediments preserved in 70% ethanol. DNA from the high-intensity pooled samples from Onye-Uku camp amplified, and a BLAST search identified the pooled samples as Schistosoma bovis, whereas S. haematobium DNA did not amplify. The phylogenetic relationship of the sequence showed that it clustered with an S. bovis hybrid obtained from a human host in Côte d'Ivoire and had close ancestry with isolates from cattle in Cameroon. This finding revealed the prevalence of S. bovis among some inhabitants in a zone in Nigeria where schistosomiasis is endemic.

Unlocking the potential of immunotherapy in platinum-resistant ovarian cancer: rationale, challenges, and novel strategies

Ovarian cancer is a significant global health challenge, with cytoreductive surgery and platinum-based chemotherapy serving as established primary treatments. Unfortunately, most patients relapse and ultimately become platinum-resistant, at which point there are limited effective treatment options. Given the success of immunotherapy in inducing durable treatment responses in several other cancers, its potential in platinum-resistant ovarian cancer (PROC) is currently being investigated. However, in unselected advanced ovarian cancer populations, researchers have reported low response rates to immune checkpoint inhibition, and thus far, no validated biomarkers are predictive of response. Understanding the intricate interplay between platinum resistance, immune recognition, and the tumour microenvironment (TME) is crucial. In this review, we examine the research challenges encountered thus far, the biological rationale for immunotherapy, the underlying mechanisms of immune resistance, and new strategies to overcome resistance.

Thermally Drawn Polymeric Catheters for MR-Guided Cardiovascular Intervention.

Cardiovascular diseases (CVDs), including congenital heart diseases (CHD), present significant global health challenges, emphasizing the need for safe and effective treatment modalities. Fluoroscopy-guided endovascular interventions are widely utilized but raise concerns about ionizing radiation, especially in pediatric cases. Magnetic resonance imaging (MRI) offers a radiation-free alternative with superior soft tissue visualization and functional insights. However, the lack of compatible instruments remains a major obstacle. An adapted thermal drawing platform that enables low-cost and rapid prototyping of instruments for MR-guided endovascular interventions is introduced. This platform is demonstrated through the development of two exemplary catheter systems: a tendon-driven steerable catheter with helical lumina and an active tracking Tiger-shaped catheter with an embedded coaxial wire. These catheters exhibit mechanical properties comparable to commercial counterparts and show promising outcomes in both in vitro and in vivo feasibility testing. This scalable thermal drawing platform addresses the limitations of existing manufacturing approaches and facilitates the exploration of diverse designs, potentially accelerating advancements in catheter technologies for MR-guided cardiovascular interventions.

Global Trends and Research Collaborations on Food and Beverages Warning Labels: A Bibliometric Analysis

Background: Non-communicable diseases (NCDs) represent a global health challenge, accounting for 74% of deaths worldwide. One of the recommended interventions to reduce the risk of NCDs is the implementation of warning labels (WLs) on food products to alert consumers about high levels of undesirable nutrients, such as sugar or saturated fats. We aimed to conduct a bibliometric analysis of scientific literature related to WL policies in food and beverages to evaluate global trends and collaborations. Methods: A bibliometric analysis was performed using the Web of Science Core Collection (WoSCC). Articles published between 1998 and 2023 were retrieved using the search terms “warning labels” AND “food” OR “beverage”. Bibliometric indicators, including publication counts, citations, collaborations, and thematic trends, were analyzed using the Bibliometrix package in R and VOSviewer. Results: We included 255 articles on WLs. Scientific production increased markedly from 2018 onwards, with over 30 articles published annually from 2018 to 2023. The most cited article, by Taillie et al., focused on the impact of Chile’s WL policies. The United States had the largest scientific production, followed by Brazil and Chile. Nutrients was the journal with the most publications on this topic. Conclusions: The growth in WL-related research, particularly in Latin America, reflects the increasing implementation of these policies. These results underscore key collaborations and evolving research themes, from food labeling to broader public health impacts, emphasizing the need for continued evaluation of WL effectiveness.

CLASSIFICATION OF COLORECTAL CANCER PATIENTS BASED ON SERUM MICRONUTRIENTS: AN EXPLORATORY INVESTIGATION

Abstract Introduction/Objective Colorectal cancer (CRC) is a growing global health challenge with a multifactorial etiology encompassing genetic susceptibility, nutrition, and inflammation in the bowel. To examine micronutrient status in CRC patients undergoing CRC resection. Methods/Case Report We performed a pilot case-control study including 13 consecutive CRC patients and 10 healthy controls (CTRL) comparing the serum levels of 29 micronutrients, namely Copper, Zinc, Selenium, Chromium, Manganese, Carnitine, Choline, Inositol, Methylmalonic acid (MMA), Vitamin (Vit) B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit C, Vit A, Vit D3, Vit E, Vit K1, Vit K2 and the amino acids Serine, Valine, Leucine, Isoleucine, Asparagine, Glutamine, Arginine, Citrulline and Cysteine. The analysis of trace metals (copper, zinc, selenium, chromium, manganese) in serum was done using the Inductively coupled plasma mass spectrometry (ICP-MS) methodology using the Agilent 8900 QQQ instrument. The analysis of serum water-soluble and fat-soluble vitamins and amino acids was conducted using the LC/MS (Xevo-TQ-XS) mass spectrometer (WBA0127). Elution of the fat-soluble vitamins was performed using a solid-phase extraction system with an OASIS Prime HLB plate containing 10 mg of sorbent per well, in a Waters vacuum manifold equipped with a waste collection plate. Comparison among continuous biological variables was carried out by multivariate ANOVA model (MANOVA), accounting for the effect of sex and age Results (if a Case Study enter NA) After considering the effect of age and sex, copper, arginine, and cysteine were increased, while zinc, selenium, chromium, Vit B1, Vit K1, and Vit A were decreased in CRC patients in comparison with CTRL. Zinc levels perfectly predicted the diagnosis of CRC, and was associated with lymph nodes (pN), of the pTNM staging. Copper levels in serum was strongly associated with the pathological pTNM staging of CRC. Conclusion Though this is a preliminary study which needs confirmation with a larger longitudinal cohort, our results show that serum micronutrients are linked to tumor growth, likely caused by increased demand from tumor tissue associated with an aberrant cell proliferation and changes in the antioxidant function.

The anticancer activity of quercetin, luteolin, myricetin, and kaempferol in the development of hepatocellular carcinoma: a narrative review

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide. It presents a significant and rising global health challenge due to its complex development, high mortality rate, and poor prognosis. The primary treatment methods include chemotherapy, radiotherapy, and surgery, yet each is associated with severe side effects. While combination therapies can enhance outcomes, they also tend to amplify the adverse effects. For this reason, the prevention of HCC has a major impact on world health. Current knowledge indicates that a healthy lifestyle combined with a healthy diet is an excellent preventive strategy. In this respect, the Mediterranean diet represents a valid preventive strategy widely recognized by the scientific community. Its effectiveness is proven by the presence of several polyphenols in its main foods, including quercetin, luteolin, myricetin, and kaempferol. These polyphenols are present in different functional foods and show anticancer activity. This narrative review aims to assess the anti-HCC activity of these polyphenols that characterize the Mediterranean diet.

Synthesis of metal nanoparticles on graphene oxide and antibacterial properties.

Pathogen-induced infections and the rise of antibiotic-resistant bacteria, such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), pose significant global health challenges, emphasizing the need for new antimicrobial strategies. In this study, we synthesized graphene oxide (GO)-based composites functionalized with silver nanoparticles (AgNPs) and copper nanoparticles (CuNPs) as potential alternatives to traditional antibiotics. The objective is to assess the antibacterial properties of these composites and explore their efficacy against E. coli and S. aureus, two common bacterial pathogens. The composites are prepared using eco-friendly and conventional methods to ensure effective nanoparticle attachment to the GO surface. Structural and morphological characteristics are confirmed through SEM, AFM, EDS, XRD, UV-vis, FTIR, and Raman spectroscopy. The antibacterial efficacy of the composites is tested through disk diffusion assays, colony-forming unit (CFU) counts, and turbidimetry analysis, with an emphasis on understanding the effects of different nanoparticle concentrations. The results demonstrated a dose-dependent antibacterial effect, with GO/AgNP-1 showing superior antibacterial activity over GO/AgNP-2, particularly at lower concentrations (32.0μg/mL and 62.5μg/mL). The GO/CuNP composite also exhibited significant antibacterial properties, with optimal performance at 62.5μg/mL for both bacterial strains. Turbidimetry analysis confirmed the inhibition of bacterial growth, especially at moderate concentrations, although slight nanoparticle aggregation at higher doses reduced efficacy. Lastly, both GO/AgNP and GO/CuNP composites demonstrated significant antibacterial potential. The results emphasize the need to fine-tune nanoparticle concentration and refine synthesis techniques to improve their efficacy, positioning these composites as strong contenders for antimicrobial use.

Quantitative Evaluation of Microcirculatory Alterations in Patients with COVID-19 and Bacterial Septic Shock through Remote Photoplethysmography and Automated Capillary Refill Time Analysis.

Background and Objectives: Sepsis, a leading global health challenge, accounts for around 20% of deaths worldwide. The complexity of sepsis, especially the difference between bacterial and viral etiologies, requires an effective assessment of microcirculation during resuscitation. This study aimed to evaluate the impact of infusion therapy on microcirculation in patients with sepsis, focusing on bacterial- and COVID-19-associated sepsis using remote photoplethysmography (rPPG) and the automated capillary refill time (aCRT). Materials and Methods: This single-center prospective study was conducted in the ICU of Pauls Stradins Clinical University Hospital, including 20 patients with sepsis/septic shock. The patients were selected based on hemodynamic instability and divided into COVID-19 and Bacterial Septic Shock groups. Fluid responsiveness was assessed using the Passive Leg Raising Test (PLRT). Systemic hemodynamics and microcirculation were monitored through MAP CRT, rPPG, and serum lactate levels. Statistical analyses compared responses within and between the groups across different stages of the protocol. Results: The Bacterial group exhibited higher initial serum lactate levels and more pronounced microcirculatory dysfunction than the COVID-19 group. rPPG was more sensitive in detecting perfusion changes, showing significant differences between the groups. The automated CRT demonstrated greater sensitivity compared to the manual CRT, revealing significant differences during PLRT stages between bacterial- and COVID-19-associated sepsis. Both groups had a transient hemodynamic response to PLRT, with subsequent stabilization upon fluid infusion. Conclusions: When managing patients with sepsis in intensive care, monitoring microcirculation is of paramount importance in infusion therapy. Our study highlights the potential of rPPG and aCRT as tools for this purpose. These techniques can be used in conjunction with routine parameters, such as lactate levels and systemic hemodynamic parameters, to provide a comprehensive assessment of a patient's condition.

Integrated Analysis of Serum and Tissue microRNA Transcriptome for Biomarker Discovery in Gastric Cancer.

Gastric cancer (GC) poses a significant global health challenge, demanding a detailed exploration of its molecular landscape. Studies suggest that exposure to environmental pollutants can lead to changes in microRNA (miRNA) expression patterns, which may contribute to the development and progression of GC. MiRNAs have emerged as crucial regulators implicated in GC pathogenesis. The largest GC serum miRNA dataset to date, comprising 1417 non-cancer controls and 1417 GC samples was used. We conducted a comprehensive analysis of miRNA expression profiles. Differential expression analysis, co-expression network construction, and machine learning models were employed to identify key serum miRNAs and their association with clinical parameters. Weighted Gene Co-expression Network Analysis (WGCNA) and immune infiltration analysis were used to validate the importance of the key miRNA. A total of 1766 differentially expressed miRNAs were identified, with miR-1290, miR-1246, and miR-451a among the top up-regulated, and miR-6875-5p, miR-6784-5p, miR-1228-5p, and miR-6765-5p among the top down-regulated. WGCNA revealed that modules M1 and M5 were significantly associated with GC subtypes and disease status. MiRNA-target gene network analysis identified prognostically significant genes TP53, EMCN, CBX8, and ALDH1A3. Machine learning models LASSO, SVM, randomforest, and XGBOOST demonstrated the diagnostic potential of miRNA profiles. Tissue and serum miR-187 emerged as an independent prognostic factor, influencing patient survival across clinical parameters. Gene expression and immune cell infiltration were different in tissues stratified by miR-187 expression. In summary, the integration of differential gene expression, co-expression analysis, and immune cell profiling provided insights into the molecular intricacies of GC progression.

Targeting AMP-activated protein kinase in sepsis.

Sepsis is a global health challenge marked by limited clinical options and high mortality rates. AMP-activated protein kinase (AMPK) is a cellular energy sensor that mediates multiple crucial metabolic pathways that may be an attractive therapeutic target in sepsis. Pre-clinical experimental studies have demonstrated that pharmacological activation of AMPK can offer multiple potential benefits during sepsis, including anti-inflammatory effects, induction of autophagy, promotion of mitochondrial biogenesis, enhanced phagocytosis, antimicrobial properties, and regulation of tight junction assembly. This review aims to discuss the existing evidence supporting the therapeutic potential of AMPK activation in sepsis management.