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PeerJ 2024The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays...
BACKGROUND
The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays emerge as valuable tools to identify and delimit malaria transmission, serving as a complementary method to rapid diagnostic tests (RDT) and thick smear microscopy. Here, we evaluate the potential of antibodies directed against peptides encompassing the entire amino acid sequence of the MSP-1 Sal-I strain as viable serological biomarkers for exposure.
METHODS
We screened peptides encompassing the complete amino acid sequence of the Merozoite Surface Protein 1 (MSP-1) Sal-I strain as potential biomarkers for exposure. Here, immunodominant peptides specifically recognized by antibodies from individuals infected with were identified using the SPOT-synthesis technique followed by immunoblotting. Two 15-mer peptides were selected based on their higher and specific reactivity in immunoblotting assays. Subsequently, peptides p70 and p314 were synthesized in soluble form using SPPS (Solid Phase Peptide Synthesis) and tested by ELISA (IgG, and subclasses).
RESULTS
This study unveils the presence of IgG antibodies against the peptide p314 in most -infected individuals from the Brazilian Amazon region. B-cell epitope prediction further supports the utilization of p314 as a potential biomarker for evaluating malaria transmission, strengthened by its amino acid sequence being part of a conserved block of MSP-1. Indeed, compared to patients infected with and uninfected individuals never exposed to malaria, -infected patients have a notably higher recognition of p314 by IgG1 and IgG3.
Topics: Humans; Malaria, Vivax; Merozoite Surface Protein 1; Plasmodium vivax; Biomarkers; Antibodies, Protozoan; Immunoglobulin G; Adult; Female; Male; Middle Aged; Peptides; Enzyme-Linked Immunosorbent Assay; Young Adult; Adolescent; Amino Acid Sequence
PubMed: 38948214
DOI: 10.7717/peerj.17632 -
PeerJ 2024Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study.
BACKGROUND
Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated.
METHODS
A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study.
RESULTS
The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure ( < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like and which might have a beneficial role in the current context and a similar decrease in species like and which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.
Topics: Humans; Male; Hypertension; Female; Middle Aged; Gastrointestinal Microbiome; Prospective Studies; Diabetes Mellitus, Type 2; Hyperglycemia; Precision Medicine; Inflammation; Proof of Concept Study; Glycated Hemoglobin; Aged; Hyperlipidemias; Adult; C-Reactive Protein
PubMed: 38948211
DOI: 10.7717/peerj.17583 -
PeerJ 2024This study aimed to assess the accuracy of Mac-2 binding protein glycosylation isomer (M2BPGi) in predicting the stage of liver fibrosis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the accuracy of Mac-2 binding protein glycosylation isomer (M2BPGi) in predicting the stage of liver fibrosis.
METHODS
Articles published until October 10, 2023, were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver-operator curves (SROC), and Spearman's rank correlation coefficient were used to examine the accuracy of M2BPGi in predicting the stage of liver fibrosis. A 95% confidence interval (CI) was provided for each estimate.
RESULTS
Twenty-four studies were included in this meta-analysis, including 3,839 patients with liver fibrosis, 409 of whom progressed to stage 4 or above. The pooled sensitivity, specificity, and area under the ROC (AUC) for M2BPGi predicting liver fibrosis ≥F3 were 0.74 (95% CI [0.65-0.82]), 0.84 (95% CI [0.76-0.89]), and 14.99 (95% CI [9.28-24.21]), respectively. The pooled sensitivity, specificity, and AUC for ≥F4 were 0.80 (95% CI [0.70-0.88]), 0.80 (95% CI [0.73-0.86]), and 16.43 (95% CI [0.84-0.90]), respectively.
CONCLUSION
Among different sample partitions, M2BPGi has the best diagnostic performance for liver fibrosis stage ≥4. Furthermore, the cutoff of 1-2 is more accurate than that of 0-1 or 2-3 for fibrosis ≥ F3 and ≥ F4.
REGISTRATION
CRD42023483260.
Topics: Humans; Liver Cirrhosis; Biomarkers; Glycosylation; Antigens, Neoplasm; ROC Curve; Sensitivity and Specificity; Membrane Glycoproteins
PubMed: 38948207
DOI: 10.7717/peerj.17611 -
PeerJ 2024Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra...
OBJECTIVE
Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra cost. However, up to now, there is not a high-quality VTE model to steadily predict the risk for VTE in China. Consequently, setting up a prediction model to predict the VTE risk is imperative.
METHODS
Data from 3,092 patients from December 15, 2017, to December 31, 2022, were retrospectively analyzed. Multiple logistic regression analysis was performed to assess risk factors for GC, and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot was created to evaluate the accuracy of the nomogram.
RESULTS
The risk factors of suffering from VTE were older age (OR = 1.02, 95% CI [1.00-1.04]), Karnofsky Performance Status (KPS) ≥ 70 (OR = 0.45, 95% CI [0.25-0.83]), Blood transfusion (OR = 2.37, 95% CI [1.47-3.84]), advanced clinical stage (OR = 3.98, 95% CI [1.59-9.99]), central venous catheterization (CVC) (OR = 4.27, 95% CI [2.03-8.99]), operation (OR = 2.72, 95% CI [1.55-4.77]), fibrinogen degradation product (FDP) >5 µg/mL (OR = 1.92, 95% CI [1.13-3.25]), and D-dimer > 0.5 mg/L (OR = 2.50, 95% CI [1.19-5.28]). The area under the ROC curve (AUC) was 0.82 in the training set and 0.85 in the validation set.
CONCLUSION
Our prediction model can accurately predict the risk of the appearance of VTE in gastric cancer patients and can be used as a robust and efficient tool for evaluating the possibility of VTE.
Topics: Humans; Nomograms; Venous Thromboembolism; Stomach Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Risk Factors; Aged; China; Risk Assessment; ROC Curve; Fibrin Fibrinogen Degradation Products; Adult
PubMed: 38948205
DOI: 10.7717/peerj.17527 -
PeerJ 2024Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible... (Review)
Review
Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible damage to the myocardium. The number of mitochondria in cardiomyocytes is large, which generate adenosine triphosphate (ATP) to sustain proper cardiac contractile function, and mitochondrial dysfunction plays a crucial role in cell death during myocardial ischemia-reperfusion, leading to an increasing number of studies investigating the impact of mitochondria on ischemia-reperfusion injury. The disarray of mitochondrial dynamics, excessive Ca accumulation, activation of mitochondrial permeable transition pores, swelling of mitochondria, ultimately the death of cardiomyocyte are the consequences of ischemia-reperfusion injury. -opioid receptors can alleviate mitochondrial dysfunction, regulate mitochondrial dynamics, mitigate myocardial ischemia-reperfusion injury, exert protective effects on myocardium. The mechanism of -OR activation during myocardial ischemia-reperfusion to regulate mitochondrial dynamics and reduce myocardial ischemia-reperfusion injury will be discussed, so as to provide theoretical basis for the protection of ischemic myocardium.
Topics: Myocardial Reperfusion Injury; Receptors, Opioid, kappa; Humans; Animals; Myocytes, Cardiac; Mitochondria, Heart; Mitochondrial Dynamics; Calcium
PubMed: 38948204
DOI: 10.7717/peerj.17333 -
PeerJ 2024Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim...
Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti- GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.
Topics: Humans; Antiphospholipid Syndrome; Retrospective Studies; Female; Atrial Fibrillation; Male; Middle Aged; Case-Control Studies; Risk Factors; Antibodies, Anticardiolipin; Adult; Aged; beta 2-Glycoprotein I; China
PubMed: 38948200
DOI: 10.7717/peerj.17617 -
Clinical Interventions in Aging 2024Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between...
Malondialdehyde and Zinc May Relate to Severity of Microvascular Complications in Diabetes: A Preliminary Study on Older Adults with Type 2 Diabetes Mellitus in Northeast China.
BACKGROUND
Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults.
METHODS
The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated.
RESULTS
There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (). Iron (r = 0.147, r = 0.180, r = 0.193, ) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (r = -0.146, ). Magnesium was positively correlated with SOD (r = 0.147, ). Zinc (r = 0.616, r = 0.575, ) was positively correlated with SOD and T-AOC. Zinc (r =-0.636, r=-0.616, ) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], ), FBG (1.265, [1.059; 1.511], ), HbAlc (1.545, [1.431; 1.680], P <0.01), MDA (2.989, [1.900; 4.702], ) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], ) and SOD (0.820, [0.698; 0.964], ) were protective factors for the severity of diabetic microvascular complications.
CONCLUSION
Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Aged; Zinc; China; Oxidative Stress; Malondialdehyde; Superoxide Dismutase; Middle Aged; Blood Glucose; Risk Factors; Diabetic Angiopathies; Glycated Hemoglobin; Nitric Oxide; Antioxidants; Magnesium; Lipids; Trace Elements; Severity of Illness Index
PubMed: 38948168
DOI: 10.2147/CIA.S464615 -
Theranostics 2024Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where...
Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model . Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. : In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.
Topics: Animals; Doxorubicin; Mice; Autophagy; Cardiotoxicity; Myocytes, Cardiac; Endoplasmic Reticulum; Membrane Proteins; Mitochondrial Proteins; Mitochondria; Mitophagy; Male; Autophagosomes; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38948070
DOI: 10.7150/thno.92771 -
Theranostics 2024Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer...
Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both and . Our findings provide an important theoretical basis for clinical prostate cancer treatment. Our and results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.
Topics: Male; Prostatic Neoplasms; Humans; Animals; Apoptosis; Histone Deacetylase Inhibitors; Cell Line, Tumor; Cell Cycle Checkpoints; cdc25 Phosphatases; Mice; Antineoplastic Agents; Cell Proliferation; Mice, Nude; Selenium; Xenograft Model Antitumor Assays; Prodrugs; Mice, Inbred BALB C
PubMed: 38948069
DOI: 10.7150/thno.92119 -
Theranostics 2024Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs...
Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation and . Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.
Topics: Animals; Extracellular Vesicles; Mesenchymal Stem Cells; Osteoporosis; Apoptosis; Mice; Female; Osteogenesis; Cell Differentiation; Mesenchymal Stem Cell Transplantation; Cell Proliferation; Mice, Inbred C57BL; Disease Models, Animal; Ovariectomy; Proteomics; Signal Transduction
PubMed: 38948067
DOI: 10.7150/thno.96174