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Simple Summary: Cortisol is a very common hormone measured when studying the stress response. While plasma cortisol is commonly utilized, concerns regarding stress caused by the sampling procedure and whether that sample represents acute vs. chronic stress have paved the way for measuring fecal cortisol metabolites (FCMs). The measurement of FCMs can be costly, and some reagents used require special permission. Commercial ELISA kits have become popular as a cost-effective method of cortisol measurement, but it is crucial to validate if these kits can detect a biologically significant change in the hormone being measured within the animal being studied. In our work, we conclude that the Arbor AssaysTM DetectX® Cortisol ELISA kit (K003-H1, Ann Arbor, MI, USA) is a reliable, economic option for the measurement of biologically relevant changes in cortisol in equine plasma and FCMs. This work helps to provide another potential tool for researchers who want to evaluate horse stress and well-being. The measurement of fecal cortisol/corticosterone metabolites (FCMs) is often used to quantify the stress response. The sampling method is relatively non-invasive, reduces concern for elevation of cortisol from the sampling method, and has been shown to measure cortisol more consistently without the daily diurnal rhythm observed in blood. Commercial ELISA (enzyme-linked immunoassay) kits offer benefits over previously validated immunoassay methods but lack validation. The objective of this study was to evaluate a commercial ELISA kit (Arbor AssaysTM DetectX® Cortisol ELISA kit, K003-H1, Ann Arbor, MI, USA) and provide analytical and biologic validation of equine fecal and plasma samples. Horses (4 male, 4 female, mean ± SD: 4 ± 5 yr) were transported for 15 min with limited physical and visual contact via a livestock trailer. Blood and fecal samples were collected pre- and post-transportation. Parallelism, accuracy, and precision tests were used to analytically validate this kit. Data were analyzed using PROC MIXED in SAS 9.4. Plasma cortisol concentrations increased in response to trailering (254.5 ± 26.4 nmol/L, 0 min post-transportation) compared to pre-transportation (142.8 ± 26.4 nmol/L). FCM concentrations increased 24 h post-trailering (10.8 ± 1.7 ng/g) when compared to pre-transportation (7.4 ± 1.7 ng/g). These data support that changes in FCMs can be observed 24 h post-stressor. In conclusion, the Arbor AssaysTM DetectX® Cortisol ELISA kit is a reliable, economic option for the measurement of biologically relevant changes in cortisol in equine plasma and FCMs. [ABSTRACT FROM AUTHOR]

The rising prevalence of tick-borne infections (TBIs) necessitates further attention. This study retrospectively investigated the types of TBIs, symptoms, and if combination antibiotics were helpful within a patient cohort at an infectious disease clinic in Ireland. In this chart audit of 301 individuals (184 female, 117 male) tested for TBIs, 140 (46.51%) had positive antibody responses for TBIs from an ELISA (enzyme-linked immunoassay) that was based on a modified two-tiered testing protocol. A total of 93 (66.43%) patients had positive antibody responses to one TBI: 83 (59.29%) for Borrelia, 7 (5.00%) for Rickettsia, and 1 (0.71%) each for either Babesia, Bartonella, or Ehrlichia. The remaining 47 (33.57%) patients were infected with multiple TBIs. These patients were treated with combination antibiotics and monitored at two subsequent follow-ups. Only 2 of 101 patients (1.98%) had discontinued treatment by the second follow-up. In the first follow-up with 118 patients, 70 (59.32%) reported pain and 48 (40.68%) had neurological symptoms. In the next follow-up of 101 patients, 41 (40.59%) had pain while 30 (29.70%) had neurological symptoms. There were statistically significant reductions in the incidence of pain (41.43%) and neurological (37.50%) symptoms between follow-ups. Thus, our study demonstrates that combination antibiotics effectively relieve TBI symptoms with good patient tolerance. [ABSTRACT FROM AUTHOR]

This study aimed to identify the polymorphism of the B Locus Beta 2 (BLB2) gene and its association with immunoglobulin Y (IgY) concentration and Newcastle disease (ND) antibody titer; we analyzed BLB2 gene expression in different categories of ND antibody titers in IPB-D2 chickens. The total sample used was 100 IPB-D2 chickens. Blood samples were collected at 21 weeks old for an ELISA (enzyme-linked immunoassay) test, an HI (hemagglutination inhibition) test, and genotyping. The method for BLB2 polymorphism was Sanger sequencing. Analysis of BLB2 gene expression was performed using the cecal tonsil tissue of IPB-D2 chickens. Polymorphism data were analyzed using SNPstats and DNAsp (DNA Sequence Polymorphism) software. The association of the single-nucleotide polymorphisms (SNPs) with IgY concentration and ND antibody titer was analyzed using SAS software (version 9.2). The genotype mean values were compared by means of a T test. The relative mRNA expression analysis was performed using a quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that 13 SNPs were found in exon 2 and exon 3 in the BLB2 gene. As many as 4 out of the 13 SNPs were associated with IgY concentration. As many as 9 out the 13 SNPs may have changed amino acids. The Δ Ct value showed that the expression of the BLB2 gene in IPB-D2 chickens with high ND antibody titers is higher than IPB-D2 chickens with low ND antibody titers. In conclusion, the AA genotype of g.458 T > A was associated with high IgY concentrations, and the BLB2 gene presented with a high expression in IPB-D2 chickens with high ND antibody titers. [ABSTRACT FROM AUTHOR]

Background: The diagnosis and treatment monitoring of hepatitis C is quite challenging. The screening test, i.e. antibody assay, is unable to detect acute cases, while the gold standard hepatitis C virus (HCV) reverse transcriptase polymerase chain reaction (RTPCR) assay is not feasible in resource-limited countries such as India due to high cost and infrastructure requirement. European Association for the Study of the Liver and World Health Organization have approved a new marker, i.e. HCV core antigen (HCVcAg) assay, as an alternative to molecular assay. In this study, we have evaluated HCVcAg assay for diagnosis and treatment monitoring follow-up in Indian population infected with hepatitis C. Methods: Blood specimen of 90 clinically suspected cases of acute hepatitis C were tested simultaneously for anti-HCV antibody assay via ELISA (enzyme-linked immunoassay), HCVcAg assay by chemiluminescence immune assay (CLIA) and HCV RTPCR VL (viral load) assay. Thirty-four HCV RTPCR positive patients were further enrolled in treatment monitoring group whose blood samples were tested at the beginning of treatment, two weeks, four weeks and 12 weeks via HCV core Ag assay and HCV RTPCR Viral Load assay. Results: Considering HCV RTPCR as gold standard, diagnostic performance of HCV core Ag assay and anti-HCV antibody assay was evaluated. The sensitivity and specificity of HCV core Ag assay were higher than that of anti-HCV Antibody assay, i.e. 88.3% and 100% vs. 23.3% and 83.3%, respectively. The overall diagnostic accuracy of HCV core Ag assay was 92.20%. Among treatment follow-up group, HCV core Ag levels correlated well with HCV viral load levels, at the beginning of treatment (baseline) till 12 weeks showing highly significant Spearman rank correlation coefficient of > 0.9 with HCV viral load levels. Conclusions: HCV core Ag assay is a cost-effective, practically feasible substitute of HCV RTPCR viral load assay for diagnosis as well as long duration treatment monitoring of hepatitis C infection in resource-limited settings. [ABSTRACT FROM AUTHOR]

Berberine‐rich extract (BRE) prepared from Berberis lycium root bark using green extraction approach and its marker compound berberine has a broad spectrum of clinical applications. Berberine's potential pharmacological effects include anticancer, antidiarrheal, antidiabetic, antimicrobial and anti‐inflammatory activities. In current work, BRE and berberine were evaluated for their therapeutic prospects in inflammation models. The comparative effect of BRE and berberine against inflammation was determined through in vitro chemiluminescence technique. The in vivo anti‐inflammatory evaluation of BRE and berberine (25, 75, and 125 mg/kg) compared to diclofenac (10 mg/kg) was performed in carrageenan and formaldehyde‐induced inflammation in Wistar rats. Histopathological and biochemical studies were conducted to find the comparative anti‐inflammatory potential of BRE and berberine on pathological hallmarks induced by formaldehyde. Moreover, the modulatory effects on inflammatory biomarkers were also investigated through qPCR. ELISA (enzyme‐linked immunoassay test assay) was performed to investigate the expression of pathological protein biomarkers like TNF‐α and IL‐6 and levels of antioxidant enzymes were estimated in liver homogenates. Both BRE and berberine markedly (p <.001) reduced paw diameter and inflammation in carrageenan and formaldehyde‐induced inflammation. The levels of antioxidant enzymes were recovered (p <.001) by BRE and berberine treatments, and compared to the formaldehyde‐treated inflammation model. Both BRE and berberine remarkably downregulated the mRNA and protein expression of inflammatory biomarkers. BRE similar to berberine mitigated the level of antioxidant enzymes in liver homogenate. The undertaken study suggests that BRE, a natural, green, and therapeutically bioequivalent to berberine could be used as an economical phytomedicine in the treatment of inflammatory disorders. Practical applications: Anti‐inflammatory drugs like NSAIDS are associated with serious adverse effects like gastrointestinal ulcer, worsening of preexisting cardiovascular disorders, and renal failure. Therefore, there is a constant demand to develop novel, inexpensive therapeutic strategies to treat the inflammatory disorder with the least harmful effects. Pure phytochemicals with anti‐inflammatory potential are costly and hard to isolate, therefore green microwave‐assisted extraction technique is developed to get the rich bioequivalent extract. Berberis lycium a medicinal plant with berberine as a major bioactive constituent, has wide acceptance in traditionally used medicine and as food. Pharmacological studies revealed its hepatoprotective, anticancer, antidiabetic, and antihypertensive activities. BRE was prepared by green microwave‐assisted extraction and enrichment by resin column to get a higher yield of berberine. The comparative anti‐inflammatory effect of BRE and berberine was determined by in vitro and in vivo studies. Results obtained from this experimental work contribute beneficial guidance that reinforces the use of the BRE to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]

There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3β-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats. Abbreviations: CAT: Catalase; GSH: Glutathione; 3β-HSD: 3β- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species. [ABSTRACT FROM AUTHOR]

An accurate diagnosis of malarial infection is an important element in combating this deadly disease. Malaria diagnostic test including, microscopy and other molecular tests are highly sensitive but too complex for field conditions. Rapid detection tests for P. falciparum infection using monoclonal antibodies (mAbs) against highly polymorphic Pf HRP2 (Histidine Rich Protein2) are still most preferred test in field conditions, but with limitations such as specificity, and sensitivity leading to false positive and false negative results. To overcome these limitations, we carried out bioinformatics analysis Pf HRP2 and Pf HRP3 and found that the C-terminal region of Pf HRP2 (~105 amino acids) displayed relatively lower sequence identity with Pf HRP3. This C-terminal region of Pf HRP2 contained unique peptide repeats and was found to be conserved in various isolates of P. falciparum . Moreover, this region was also found to be highly antigenic as predicted by antigenicity propensity scores. Thus we constructed a cDNA clone of the truncated Pf HRP2 (rec Pf HRP2-T3) coding for C-terminal 105 amino acids and expressed it in E. coli and purified the polypeptide to homogeneity. The purified rec Pf HRP2-T3 was used as an antigen for development of both polyclonal and monoclonal antibody (mAb). The mAbs b10c1 and Aa3c10 developed against rec Pf HRP2-T3 was found to efficiently recognize recombinant Pf HRP2 but not Pf HRP3. In addition, the above mAbs reacted positively with spent media and serum sample of P. falciparum infection recognizing the native Pf HRP2. The affinity constant of both the clones were found to be 10 9  M −1 . Quantitatively, both these clones showed ~4.4 fold higher reactivity with P. falciparum infected serum compared to serum from healthy volunteers or P. vivax infected patient samples. Thus these anti-C-terminal Pf HRP2 mAbs (Aa3c10 and b10c1) display a very high potential for improvising the existing malarial diagnostic tools for detection of P. falciparum infection especially in areas where Pf HRP2 polymorphism is highly prevalent. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other. Abbreviations: AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients [ABSTRACT FROM AUTHOR]

Background On 12 June 2020, Brazil reached the second position worldwide in the number of COVID-19 cases. Authorities increased the number of tests performed, including the identification of antibodies to SARS-CoV-2 (IgG, IgA, and IgM). There was an overflooding of the market with several tests, and the presence of possible false-positive results became a challenge. The purpose of this study was to describe the seroprevalence and immunoglobulin blood levels in a group of asymptomatic individuals using the reference levels provided by the manufacturer. Methods Levels of IgG and IgA antibodies to SARS-CoV-2 were determined in blood serum by the same ELISA (enzyme-linked immunoassay) test. Patients must be free of symptoms. Results: From 20 to 22 May 2020, 938 individuals were tested. There were 441 (47%) men, age 53 years (interquartile range (IQR) = 39-63.2). The sample included 335 (35.7%) subjects aged >60 years old. Subjects with a positive test were 54 (5.8%) for IgG and 96 (10.2%) for IgA and 42 (4.5%) for both IgG and IgA. The prevalence of IgG and IgA positive test was not different in men and women and not different in individuals under 60 and over 60 years of age. Conversely, analysing only individuals with positive tests, the levels of IgG in positive subjects were significantly higher than those with an IgA positive test, 3.00 (IQR= 1.68-5.65), and 1.95 (IQR = 1.40-3.38), respectively; P = 0.017. Additionally, individuals with isolated IgA positive tests had significantly lower levels of IgA than those with both IgA and IgG positive tests: 1.95 (IQR = 1.60-2.40) and 3.15 (IQR = 2.20-3.90), respectively, P = 0.005. These latter data suggest that IgA shows a deviation of the distribution to the left in comparison to IgG distribution data. Indeed, many subjects reported as IgA positive had immunoglobulin levels slightly elevated. Conclusions In conclusion, we strongly suggest caution in the interpretation of IgA test results. This recommendation is more important for those with positive IgA just above the reference level. [ABSTRACT FROM AUTHOR]

The repertoire of antibodies producing by immunizing rabbits with cobrotoxin and dimeric glutaraldehyde-modified cobrotoxin (dGA-cobrotoxin) was analyzed by studying the immunoreactivity of the two antibody preparations toward cobrotoxin, GA-cobrotoxin and recombinant cobrotoxin. The results of enzyme-linked immunoassay revealed that the two antibody preparations exhibited a higher reactivity against their cognate antigen. Moreover, different behavior was observed for the reactivity of the two antibody preparations against GA-cobrotoxin and recombinant cobrotoxin. Notably, distortion of disulfide linkages at the C-terminus resulted in a reduced decrease in the antigenic activity of recombinant cobrotoxin toward anti-cobrotoxin antibodies compared to anti-dGA-cobrotoxin antibodies. Affinity purification of the antibodies against the C-terminus of cobrotoxin revealed that its amount represented 77% and 35.5% of the total anti-dGA-cobrotoxin antibodies and the total anti-cobrotoxin antibodies, respectively. These findings suggest that the antibody preparation elicited by dGA-cobrotoxin enriches the content of antibodies recognizes the C-terminal region of native cobrotoxin. [Copyright &y& Elsevier]

Helicobacter pylori (H. pylori) infection is linked to metabolic syndrome and insulin resistance, with the triglyceride-glucose (TyG) index serving as a reliable marker for the latter. This study investigates the association between the TyG index and H. pylori infection. The study utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2000. Participants underwent serologic testing for H. pylori, and the TyG index was calculated from fasting laboratory measurements. Multivariate logistic regression and restricted cubic spline methods were used to assess the association and explore the dose–response relationship. The analysis included 2984 participants. Elevated TyG index values were associated with an increased likelihood of H. pylori infection. The risk of infection rose with higher TyG index quartiles, with the highest quartile showing the most significant increase (OR = 1.54, 95% CI: 1.15–2.07, P = 0.004). A linear relationship between the TyG index and H. pylori infection was demonstrated. The study findings indicate a significant positive association between the TyG index and H. pylori infection. This association highlights the importance of metabolic health in the context of H. pylori infection and suggests that further research is needed to explore the potential implications for health promotion strategies. [ABSTRACT FROM AUTHOR]

Melatonin is vital in human circadian rhythm and infant development. This scoping review summarized the current knowledge about melatonin's presence and effects in human milk to promote better understanding of its secretion pattern and clinical advancement of maternal-infant health. The review followed the Joanna Briggs Institute guideline and answered the question: What is the current knowledge about melatonin hormone in human milk? The databases searched were PubMed, CINAHL, SCOPUS, Web of Science, LILACS, Scielo, EMBASE, Science Direct, Eric, Cochrane, in addition to grey literature and reference lists of included sources. Research papers included English, Spanish, or Portuguese languages, regardless of study type or publication date. The study selection and data extraction involved two independent reviewers. Twenty-nine studies met inclusion criteria. The studies, conducted between 1993 and 2023, employed diverse designs, with cross-sectional studies being the most prevalent. Melatonin concentration exhibited a consistent pattern, being higher at night, and elevated in colostrum. The analysis methods for melatonin concentration evolved, with recent advancements contributing to more accurate measurements. Factors influencing melatonin levels, such as delivery type, maternal age, and health conditions, demonstrated a complex relationship, potentially impacting the health and development of infants. The dynamic nature of melatonin in human milk calls for continued interdisciplinary research, bridging gaps between clinical, biochemical, and epidemiological perspectives. Standardizing melatonin analysis methods are needed. Nurses should assess factors influencing melatonin levels in milk to promote interventions and guidance aimed at enhancing the regulation of the circadian cycle during the perinatal period and its benefits. [ABSTRACT FROM AUTHOR]

Tetrodotoxin (TTX) is a neurotoxin that binds to sodium channels and blocks sodium conduction. Importantly, TTX has been increasingly detected in edible aquatic organisms. Because of this and the lack of specific antidotes, TTX poisoning is now a major threat to public health. However, it is of note that ultra-low dose TTX is an excellent analgesic with great medicinal value. These contradictory effects highlight the need for further research to elucidate the impacts and functional mechanisms of TTX. This review summarizes the latest research progress in relation to TTX sources, analogs, mechanisms of action, detection methods, poisoning symptoms, therapeutic options, biosynthesis pathways, and mechanisms of transport and accumulation in pufferfish. This review also provides a theoretical basis for reducing the poisoning risks associated with TTX and for establishing an effective system for its use and management to ensure the safety of fisheries and human health. [ABSTRACT FROM AUTHOR]

Background/Objectives: The acute phase of stroke is marked by inflammation and mobility changes that can compromise nutritional status. This study was a randomized, double-blind, placebo-controlled trial evaluating the effectiveness of creatine supplementation for older people during seven days of hospitalization for stroke compared to usual care. Method: The primary outcome measures were changes in functional capacity, strength, muscle mass, and muscle degradation. The secondary outcomes were changes in serum biomarkers related to inflammation, fibrosis, anabolism, and muscle synthesis. In addition, a follow-up 90 days after the stroke verified functional capacity, strength, quality of life, and mortality. Following admission for an acute stroke, participants received either creatine (10 g) or a visually identical placebo (10 g) orally twice daily. Both groups received supplementation with protein to achieve the goal of 1.5 g of protein/kg of body weight/day and underwent daily mobility training during seven days of hospitalization. Results: Thirty older people were included in two similar groups concerning baseline attributes (15—treatment/15—placebo). Conclusions: Creatine supplementation did not influence functional capacity, strength, or muscle mass during the first 7 days or outcomes 90 days after stroke. There were no serious adverse events associated with creatine supplementation. However, it decreased progranulin levels, raising a new possibility of creatine action. This finding needs further exploration to understand the biological significance of creatine–progranulin interaction. [ABSTRACT FROM AUTHOR]

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Background/Aims: Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. Methods: We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed. Results: IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing β-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs. Conclusion: Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Dengue is the most important arboviral disease, and Aedes aegypti and Aedes albopictus are the major vectors. It is one of the most recent emerging diseases in Mizoram state with a fast-growing burden over the years. The present study aimed to explore the epidemiological patterns of dengue in Mizoram, and to identify vector mosquito species. Methods: In the present study, two years secondary data of dengue disease in Mizoram was studied. Dengue vector mosquitoes and dengue virus serotypes circulating in vector mosquitoes in Aizawl City were identified by sequence analysis of COX1 and C-prM genes respectively. Results: In Mizoram State, the annual case prevalence of dengue was found to be 300.45 per 100,000 persons. Seasonality of the disease was also noted, with the peak season occurring from July to December. There is a significant positive relationship between age and the disease prevalence (p < 0.05, r = 0.909). DENV was detected in 10 pools of Ae. aegypti with a minimum infection rate (MIR) of 18.05, and 8 pools of Ae. albopictus with a minimum infection rate of 16.03. The viral isolates were found to correspond to serotypes 2 (DENV2) and 3 (DENV3). A total of 6 pools of Aedes aegypti and 4 pools of Aedes albopictus tested positive with DENV2 serotype, while 4 pools of Aedes aegypti and 3 pools of Aedes albopictus tested positive with DENV3 serotype. DENV2 serotype was more common, and multiple serotypes (DENV2 and DENV3) were also detected in two pools from one locality. Conclusions: There is an increasing trend in dengue infection in Mizoram, and seasonality of the disease was observed with the peak season during July to December. The higher incidence rate among the adults indicated that outdoor activities may be related to the high risk of the infection. However, lack of immunity among the older people may also be a possible reason of higher disease incidence rather than the activity pattern. Early identification and frequent monitoring of infected vector mosquitoes will yield an early warning indicator for forecasting dengue epidemics in the future. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need. We previously discovered that hyperactivating purinergic receptors (P2RXs) by increasing extracellular adenosine triphosphate (eATP) concentrations enhances TNBC cell lines' response to chemotherapy. Heparan sulfate inhibits multiple extracellular ATPases, so it is a molecule of interest in this regard. In turn, heparanase degrades polysulfated polysaccharide heparan sulfate. Importantly, previous work suggests that breast cancer and other cancers express heparanase at high levels. Hence, as heparan sulfate can inhibit extracellular ATPases to facilitate eATP accumulation, it may intensify responses to chemotherapy. We postulated that heparanase inhibitors would exacerbate chemotherapy-induced decreases in TNBC cell viability by increasing heparan sulfate in the cellular microenvironment and hence, augmenting eATP. Methods: We treated TNBC cell lines MDA-MB 231, Hs 578t, and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells with paclitaxel (cytotoxic chemotherapeutic) with or without the heparanase inhibitor OGT 2115 and/or supplemental heparan sulfate. We evaluated cell viability and the release of eATP. Also, we compared the expression of heparanase protein in cell lines and tissues by immunoblot and immunohistochemistry, respectively. In addition, we examined breast-cancer-initiating cell populations using tumorsphere formation efficiency assays on treated cells. Results: We found that combining heparanase inhibitor OGT 2115 with chemotherapy decreased TNBC cell viability and tumorsphere formation through increases in eATP and activation of purinergic receptors as compared to TNBC cells treated with single-agent paclitaxel. Conclusion: Our data shows that by preventing heparan sulfate breakdown, heparanase inhibitors make TNBC cells more susceptible to chemotherapy by enhancing eATP concentrations. [ABSTRACT FROM AUTHOR]

The gut microbiome influences neurological disorders through bidirectional communication between the gut and the brain, i.e., the gut-brain axis. Artemisia asiatica ex, an extract of Artemisia asiatica Nakai (Stillen®, DA-9601) has been reported to improve depression by increasing brain-derived neurotropic factor. Therefore, we hypothesized that DA-9601 can be a potential therapeutic candidate for Alzheimer's disease (AD) acting through the gut-brain axis. Four groups of Tg2576 mice were used as the animal model for AD: wild type mice (n = 6), AD mice (n = 6), and DA-9601-administered AD mice given dosages of 30mg/kg/day (DA_30mg; n = 6) or 100mg/kg/day (DA_100mg; n = 6). Microglial activation, blood‒brain barrier integrity, amyloid beta accumulation, cognitive behavior, and changes in the gut microbiome were analyzed. DA-9601 improved the cognitive behavior of mice (DA_30mg **p<0.01; DA_100mg **p<0.01) and reduced amyloid beta accumulation (DA_30mg ***p<0.001; DA_100mg **p<0.01). Increased Iba-1 and upregulation of claudin-5 (DA_30mg *p<0.05) and occludin (DA_30mg **p<0.01; DA_100mg ***p<0.001) indicated altered microglial activation and improved blood‒brain barrier integrity. Akkermansia muciniphila was dramatically increased by DA-9601 administration (DA_30mg 47%; DA_100mg 61%). DA-9601 improved AD pathology with Akkermansia muciniphila dominance in the gut microbiome in a mouse model of AD, inferring that DA-9601 can affect AD through the gut-brain axis. [ABSTRACT FROM AUTHOR]

Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25–1.68]; blood: 1.35 [1.09–1.60]) and NFH (CSF: 1.32 [1.13–1.50], blood: 0.90 [0.58–1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations. [ABSTRACT FROM AUTHOR]

Background: Hydatid disease, also known as echinococcosis, is an endemic parasitic infection, most commonly caused by Echinococcus granulosus. It may affect any organ resulting in the formation of hydatid cysts, but most frequently involves liver and lungs. Hydatid cyst arising primarily from axilla is an extremely rare manifestation of this condition, with only a few cases reported in medical literature. Case presentation: Here we present the case of a 32-year-old Indian male farmer, who presented with a painless, slow-growing mass in the left axillary region of 8 months duration. Preoperative imaging led us to the diagnosis of primary axillary hydatid cyst, with no other associated cysts or masses anywhere else in the body. Following antihelmintic therapy, the cyst was surgically excised without rupture. The diagnosis was further confirmed by macroscopic and histopathological examination. Conclusion: This case report highlights the importance of considering hydatid cyst in the differential diagnosis of palpable masses in the axillary region, especially in regions where the disease is endemic. Early recognition and accurate diagnosis are crucial for appropriate management and optimal patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Yellow fever virus (YFV) and dengue virus (DENV) are among the major re-emerging arboviruses that pose a significant threat to public health. Their associated burden and prevalence can be substantially underestimated due to insufficient surveillance and inadequate diagnosis. This study aimed to determine evidence of dengue, yellow and related flaviviruses circulation among the rural human populations residing in Nguruman (Kajiado County) and Kerio Valley (Baringo County), two dryland ecosystems in the Kenyan Rift Valley. Methods: Serum samples obtained from febrile patients between 5 and 85 years through a hospital-based cross-sectional survey from July 2020 – May 2023, were screened for neutralizing antibodies to YFV, DENV-2 and related flaviviruses, West Nile virus (WNV) and Zika virus (ZIKV) via Plaque reduction neutralization test (PRNT). The study sites and important demographic characteristics were obtained using a structural questionnaire and the data analyzed and seroprevalence compared. A multinomial logistic regression model was done to predict risk for each of the most prevalent viruses with covariates; age, gender, and occupation. Results: Overall, 54.5% (50.1–59.0% 95% confidence interval (CI) of the samples tested positive for at least one of the four Flaviviruses. The percentage was significantly higher in Kerio Valley (64.34%, 184/286) than in Nguruman (40.2%, 78/194) (P<0.0001). YFV had the highest prevalence, followed by WNV (16.25%), ZIKV (5.2%), and DENV-2 (1%). Kerio Valley had a significantly higher YFV seroprevalence (51%) than Nguruman (6%) (P<0.0001), while DENV-2 was observed only in Nguruman with a low seropositivity of 2%. In contrast to Nguruman, where seropositivity rates were higher in males at 47.47% (P=0.049), in Kerio Valley, females showed considerably higher viral seropositivity at 60.82% than males (P<0001). Conclusion: The study suggests that there is significant circulation of Flaviviruses in both regions, posing a public health risk, that could potentially contribute to clinical disease. However, seropositivity rates vary for each specific site. Furthermore, there could be a risk of YFV, WNV, and ZIKV transmission in both sites with DENV transmission specifically noted in Nguruman. The study findings inform direct cost-effective actions (such as YF vaccines) and precise surveillance data of vector populations for improved disease risk prediction. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a disease caused by the intracellular protozoan Toxoplasma gondii, which has infected a third of the global population. Immunocompromised individuals and children with congenital disorders are most likely to be impacted by toxoplasmosis, and accurate diagnosis is essential. Toxoplasmosis is associated with HIV, schizophrenia, and diabetes. However, few studies have analyzed the association with other microorganisms. The purpose of this study was to determine the prevalence of coinfection of Toxoplasma gondii with other pathogens. From November 1997 to June 2024, PubMed, Science Direct, LAT index, Web of Science, Google Scholar, and Research Gate were searched. The keywords used were "Toxoplasma and microorganism coinfection", "Toxoplasma coinfection and parasites", "Toxoplasma coinfection and Protozoans or Bacteria or Helminths or Nematodes or Trematodes or Mycobacterium", "Toxoplasma gondii in coinfection with virus", and "Human Toxoplasmosis and coinfection". Next, OpenMeta Analyst Software version 12.11 was used for meta-analysis, creating forest plots, and determining heterogeneity I2. A total of 17,535 patients in 48 articles, of whom 5848 were seropositive to T. gondii, were included in this review. Population studies showed that the prevalence of virus infection was most frequent (32%), followed by parasites (18.4%), bacteria (29.7%), and fungi (5.8%). The pooled prevalence of coinfection was found to be 29.1%, with a lower bound of 0.232, an upper bound of 0.350, a standard error of 0.030, and p < 0.001. Heterogeneity (I2) was 99.12%, p < 0.001, with a global variance tau2 = 0.042. Toxoplasma gondii is an opportunist that mainly affects immunocompromised populations. The main coinfections were found to be viral infections, with HIV ranking first, followed by cytomegalovirus, hepatitis B and C, rubella, herpes simplex 1 and 2, SARS-CoV-2, and coxsackie virus. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an intracellular parasite capable of crossing the placenta in pregnancy and infecting the developing fetus, leading to various congenital anomalies and even abortion. Acute Toxoplasma infection is responsible for almost all cases of congenital toxoplasmosis in immunocompetent pregnant women. Prenatal screening for acute toxoplasmosis primarily involves maternal serology and fetal ultrasound imaging. When serological or ultrasound findings suggest acute infection, further diagnostic tests are necessary to confirm fetal infection. Currently, molecular methods to detect the parasite's DNA, including polymerase chain reaction-based methods, on amniotic fluid are the gold standard tests for the diagnosis of congenital toxoplasmosis. In this review, we aim to discuss various aspects of screening and diagnostic methods for toxoplasmosis in pregnancy, including (i) current serological assays, screening approaches, and future perspectives; (ii) the role of imaging techniques, with an emphasis on ultrasound; (iii) principles and recent advances in diagnostic molecular methods; (iv) emerging techniques, such as point-of-care-based tests and biosensors, and microRNAs as novel biomarkers of acute infection; and (v) an overview of screening programs in different countries, important epidemiological determinants, and recommendations for Toxoplasma screening health policies. [ABSTRACT FROM AUTHOR]

Clinical studies have found there still exists a lack of gene therapy dose-toxicity and dose-efficacy data that causes gene therapy dose selection to remain elusive. Model informed drug development (MIDD) has become a standard tool implemented throughout the discovery, development, and approval of pharmaceutical therapies, and has the potential to inform dose-toxicity and dose-efficacy relationships to support gene therapy dose selection. Despite this potential, MIDD approaches for gene therapy remain immature and require standardization to be useful for gene therapy clinical programs. With the goal to advance MIDD approaches for gene therapy, in this review we first provide an overview of gene therapy types and how they differ from a bioanalytical, formulation, route of administration, and regulatory standpoint. With this biological and regulatory background, we propose how MIDD can be advanced for AAV-based gene therapies by utilizing physiological based pharmacokinetic modeling and quantitative systems pharmacology to holistically inform AAV and target protein dynamics following dosing. We discuss how this proposed model, allowing for in-depth exploration of AAV pharmacology, could be the key the field needs to treat these unmet disease populations. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) originating from monocytes are crucial for cancer progression; however, the mechanism of TAM differentiation is unclear. We investigated factors involved in the differentiation of monocytes into TAMs within the tumor microenvironment of triple-negative breast cancer (TNBC). We screened 172 compounds and found that a heat shock protein 90 (HSP90) inhibitor blocked TNBC-induced monocyte-to-TAM differentiation in human monocytes THP-1. TNBC-derived conditional medium (CM) activated cell signaling pathways, including MAP kinase, AKT and STAT3, and increased the expression of TAM-related genes and proteins. These inductions were suppressed by HSP90 inhibition or by knockdown of HSP90 in TNBC. Additionally, we confirmed that TNBC secreted HSP90 extracellularly and that HSP90 itself promoted TAM differentiation. In a mouse tumor model, treatment with an HSP90 inhibitor suppressed tumor growth and reduced TAMs in the tumor microenvironment. Our findings demonstrate the role of HSP90 in TAM differentiation, suggesting HSP90 as a potential target for TNBC immunotherapy due to its regulatory role in monocyte-to-TAM differentiation. [ABSTRACT FROM AUTHOR]

Nearly 60 million people worldwide are infected with Hepatitis C Virus (HCV), a bloodborne pathogen which leads to liver cirrhosis and increases the risk of hepatocellular carcinoma. Those with limited access to healthcare resources, such as injection drug users and people in low- and middle-income countries, carry the highest burden. The current diagnostic algorithm for HCV is slow and costly, leading to a significant barrier in diagnosis and treatment for those most at risk from HCV. There remains no available vaccine for HCV, and infection is often asymptomatic until significant cirrhosis has occurred, which makes screening incredibly important to prevent liver damage and transmission. Recent investigation has sought to address these issues through improvements in various aspects of the diagnostic procedure, using methods such as isothermal amplification techniques for viral RNA amplification, the use of viral protein as an analyte, and the incorporation of streamlined, self-contained testing systems to reduce administrative skill requirements. This review provides a comprehensive overview of current commercial standards and novel improvements in HCV diagnostics, as well as a framework for future integration of these improvements to develop a one-step diagnostic that meets the needs of those most affected. [ABSTRACT FROM AUTHOR]

Background: Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania. Methods: The number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023. Results: We estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018−2020 (86.0) and higher than in 2021−2022 (40.3). Conclusions: There is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB. [ABSTRACT FROM AUTHOR]

Enzymes play a crucial role in enhancing food processing techniques and improving flavor quality. They are also used for prolonging the storage period and rapid detection of foodborne diseases, essential for ensuring food quality and safety. With the rapid development of the food industry, the application prospects of enzymes have become increasingly prominent. In this review, the applications of enzymes in food processing, preservation, and detection were expounded in detail, and further attention is paid to the processing points and application effects of enzymes in all aspects of food production. The research and application direction of enzymes in the future were also speculated to help interested parties to understand the application advantages and prospects of enzymes. [ABSTRACT FROM AUTHOR]

Many individuals with systemic lupus erythematosus (SLE) face significant challenges manifesting their family planning goals due to numerous factors, including disease-related complications, treatment-induced effects, immunological factors, self-imposed limitations, and the socioeconomic impacts of having a chronic disease. Instances of unexplained infertility are also prevalent. Encouragingly, advancements in treatment modalities, risk factor management, specialized training within the medical community, and enhanced patient/provider education have contributed to an increase in successful pregnancies among SLE patients, fostering a safer, more promising reproductive landscape. However, despite advances, individuals with SLE continue to struggle with the complexities of family building. This review explores infertility and pregnancy outcomes in SLE, fertility preservation, the role of assisted reproductive technology, and considerations for tailoring these approaches to SLE patients. [ABSTRACT FROM AUTHOR]

The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway. [ABSTRACT FROM AUTHOR]

We presented the validation method of the quantitative determination of Nitrofuran (AOZ) and Chloramphenicol in honey samples by the RidaScreen® test system (according to Commission Decision 2002/657/EC and Guidelines for the validation of screening methods for residues of veterinary medicines (initial validation and transfer) of 20/01/2010). We revealed several validation indicators like ccβ (detection capability), accuracy (precision), recovery and some others during the initial validation (specificity and selectivity). We determined the minimum detection values of Nitrofuran (AOZ) in honey, the highest value (the highest response) for blank samples is 0.066 μg/kg and the lowest value for enriched samples (lowest response) is 0.401 μg/kg. Based on the obtained results none of the responses for enriched samples do not coincide with the range of replies of blank samples. Hence, it follows that the detection capability (CCβ) for this screening method is less than or equal to 0.4 μg/kg. For the determination of Chloramphenicol, the highest response is noted for blank samples – 0.021 μg/kg (21 ng/kg) and the lowest response noted for enriched samples is 0.048 μg/kg (48 ng/kg). None of the responses for enriched samples do not coincide with the range of replies of blank matrix (samples), therefore we could conclude that the CCβ of this screening method is less than or equal to 0.05 μg/kg (β-error < 5 %) and the cut-off value of this test is 0.048. According to the validation the lowest value of substances that could detected by ELISA using the following test systems for competitive ELISA (enzyme-linked immunoassay) for Nitrofuran (AOZ) – 0.4 μg/kg, for Chloramphenicol – 0.05 μg/kg. Described in State Standard 4497:2005 “Natural Honey. Technical conditions” the maximum allowable level for Chloramphenicol – 0.3 μg/kg and Nitrofuran (AOZ) – 0.6 μg/kg require correction according to the established validation parameters. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has recently gained relevance in treating different psychiatric disorders. Limited evidence suggests that the beneficial effects of rTMS on psychopathology could be at least partly mediated through changes in inflammatory response. This systematic review summarizes the literature on whether rTMS can modulate inflammatory markers and thus positively influence the course of psychiatric illnesses. Materials and methods: A systematic review of rTMS and inflammatory markers in psychiatric diseases was conducted according to PRISMA guidelines. Information on the association between rTMS treatment response and changes of inflammatory markers was extracted. The quality of the studies was assessed using the National Heart, Lung, and Blood Institute for human studies and the Systematic Review Center for Laboratory Animal Experimentation for animal studies. Results: This review includes 17 studies (2 animal and 15 human studies) on the relationship between rTMS treatment response and changes of inflammatory markers. Positive changes in microglial activity and anti-inflammatory effects were associated with behavioral improvement in animal models of depression. However, these findings have not been consistently replicated in human studies focusing on treatment-resistant depression. While several studies reported rTMS-induced alterations in peripheral inflammatory markers, only two could demonstrate their association to clinical treatment response. Notably, most studies showed poor or moderate quality in the bias assessment. Conclusions: While certain human studies suggest an association between rTMS-induced anti-inflammatory effects and improvement in psychopathology, heterogeneity, and underpowered analyses constrain the generalizability of these results. The discrepancy between animal and human findings highlights the need for larger, standardized human studies. Trial registration: (PROSPERO Registration: CRD42023492732). [ABSTRACT FROM AUTHOR]