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1.
EClinicalMedicine ; 68: 102364, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38586479

RESUMO

Background: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population). Interpretation: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding: Renibus Therapeutics, Inc.

2.
Sci Total Environ ; 927: 172088, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554975

RESUMO

Microplastics (MPs) is the second most important environmental issue and can potentially enter into food chain through farmland contamination and other means. There are no standardized extraction methods for quantification of MPs in soil. The embedded errors and biases generated serious problems regarding the comparability of different studies and leading to erroneous estimation. To address this gap, present study was formulated to develop an efficient method for MPs analysis suitable for a wide range of soil and organic matrices. A method based on Vis-NIR (Visible-Near Infra Red) spectroscopy is developed for four different soil belonging to Alfisol, Inceptisol, Mollisol and Vertisol and two organic matter matrices (FYM and Sludge). The developed method was found as rapid, reproducible, non-destructive and accurate method for estimation of all three-density groups of MPs (Low, Medium and High) with a prediction accuracy ranging from 1.9 g MPs/kg soil (Vertisol) to 3.7 g MPs/kg soil (Alfisol). Two different regression models [Partial Least Square Regression (PLSR) and Principal Component Regression (PCR)] were assessed and PLSR was found to provide better information in terms of prediction accuracy and minimum quantification limit (MQL). However, PCR performed better for organic matter matrices than PLSR. The method avoids any complicated sample preparation steps except drying and sieving thus saving time and acquisition of reflectance spectrum for single sample is possible within 18 s. Owing to have the minimum quantification limit ranging from 1.9-3.7 g/kg soil, the vis-NIR based method is perfectly suitable for estimation of MPs in soil samples collected from plastic pollution hotspots like landfill sites, regular based sludge amended farm soils. Additionally, the method can be adapted by small scale compost industries for assessing MPs load in product like city compost which are applied at agricultural fields and will be helpful in quantifying possible MPs at the sources itself.

3.
Cardiol Rev ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441154

RESUMO

Music therapy (MT) is a music intervention involving a credentialed professional and a client, which has gained increasing recognition in current practices as an adjunct therapy for various conditions, including cardiovascular diseases (CVDs). MT demonstrates notable physiological as well as psychological effects leading to lowered anxiety, depression, and systolic blood pressure in patients with CVDs as well as having effects on heart rate and heart rate variability in healthy subjects. MT emerges as a promising adjunct in the prevention and rehabilitation of CVDs and its holistic impact on physiological and psychological parameters underscores its potential as a noninvasive, cost-effective intervention. Existing literature shows heterogeneity in methods in the studies such as the genre and quality of music utilized as well outcomes. While further research is warranted to optimize protocols and assess long-term effects, the current evidence highlights MT's substantial benefits in cardiovascular health care, making it a promising asset in modern therapeutic approaches. This comprehensive review explores the multifaceted role of MT in CVDs, discussing its mechanisms and clinical applications.

4.
Cardiol Rev ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445894

RESUMO

Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.

5.
South Med J ; 117(3): 159-164, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428938

RESUMO

OBJECTIVES: Pancreatic divisum (PD) is the second most common congenital abnormality of the pancreatic duct, which affects 2% to 3% of the population. Most of the population remains asymptomatic, but in people who present with symptoms, it can be a cause of anguish and should be recognized. The main goal of this article was to provide a comprehensive picture of clinical and epidemiological methods of diagnosis and treatment of PD. METHODS: A total of 57 PD case reports were considered in this descriptive analysis with 51 case reports and case series published within the last 25 years. The search strategies include systemic searches using scholarly search engines such as Medscape, Scopus, Cochrane, and PubMed. RESULTS: The 57 cases we studied have an average age of presentation of 42 years, with female sex (58%) predominance. Common presenting symptoms were abdominal pain (87.72%) and radiation to the back (21.6%). Eighty-one percent of the case studies reported pancreatitis, and 63.2% had recurrent pancreatitis. At presentation, laboratory values demonstrated increased amylase, lipase, and liver enzymes. PD was diagnosed using magnetic resonance cholangiopancreatography (28.1%), endoscopic retrograde cholangiopancreatography (57.9%), endoscopic ultrasound (7%), or computed tomography (5.3%) scan of the abdomen. Of significance, biliary duct dilation was found in 70.6% of patients diagnosed as having PD. Incidental masses were found in 66.7% of the patients. The most successful treatment was sphincterotomy with or without stents (47.6%), followed by pancreatoduodenectomy (19%) and pancreaticojejunostomy (10%). CONCLUSIONS: Physicians managing pancreatitis should add PD to their differential diagnoses because it will help improve patient outcomes and avoid unfavorable consequences.


Assuntos
Pâncreas Divisum , Pancreatite , Humanos , Feminino , Adulto , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Ductos Pancreáticos/anormalidades , Dor Abdominal/etiologia
6.
Int J Pharm ; 654: 123936, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417727

RESUMO

Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-)8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands. Failure mode effect analysis and factor screening studies were performed to identify concentrations of SPIONs and ligand as critical material attributes, and systematic optimization was subsequently conducted employing face-centered cubic design. The optimum formulation was delineated using desirability function, and design space demarcated with 178.70 nm as hydrodynamic particle size, -24.40 mV as zeta potential, and 99.89 % as hydrophilic iron content as critical quality attributes. XRD patterns ratified lattice structure and SQUID studies corroborated superparamagnetic properties of hydrophilic SPIONs. Bioconjugation of (-D-Asp-)8 with SPIONs (1:1) was confirmed using UV spectroscopy, FTIR and NMR studies. Cell line studies indicated successful targeting of SPIONs to MG-63 human osteoblasts, ratifying enormous bone-targeting and safety potential of peptide-tethered SPIONs as MRI probes. In vivo MRI imaging studies in rats showcased promising contrast ability and safety of peptide-conjugated SPIONs.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Osteoporose , Ratos , Humanos , Animais , Nanopartículas de Magnetita/química , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Nanopartículas Magnéticas de Óxido de Ferro , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Nanopartículas/química
7.
Cardiol Rev ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385663

RESUMO

The use of e-cigarettes has tremendously increased in recent times due to the widespread availability of e-cigarettes in diverse flavors, reduced cost compared to regular cigarettes, and misconception of being comparatively safe, which have led to around 2.55 million US middle and high school students smoking e-cigarettes. These devices use a nicotine-rich liquid, which is aerosolized electronically, producing vapors that may also include hazardous chemicals and heavy metals. E-cigarettes are associated with e-cigarette or vaping-associated lung injury, which presents as an acute respiratory ailment mirroring various pulmonary diseases. Additionally, it causes endothelial dysfunction, alters blood lipid profile by elevating circulating levels of low-density lipoprotein cholesterol, increases sympathetic tone, and is found to correlate with arterial stiffening, hence negatively affecting respiratory, cardiovascular, and overall health. We aim to provide a comprehensive analysis of the data on e-cigarettes and their harmful effects on health in comparison to conventional cigarette use by highlighting the pathophysiology of e-cigarette-induced adverse effects and critically analyzing the data both in favor and against its use. Our review concludes that no matter how much nicotine an e-cigarette contains, evidence shows that using it increases the risk of cardiovascular disease, albeit maybe not as much as smoking regular tobacco. Nonetheless, it is crucial to note that the long-term effects of e-cigarette usage are still not fully understood, and existing data have provided opposing viewpoints.

8.
Plant Physiol Biochem ; 207: 108336, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38245990

RESUMO

Iron (Fe) is an essential plant nutrient that is indispensable for many physiological activities. This study is an effort to identify the molecular and biochemical basis of wheat genotypes with contrasting tolerance towards Fe deficiency. Our physiological experiments performed at the early growth stage in cv. Kanchan (KAN) showed Fe deficiency tolerance, whereas cv. PBW343 (PBW) was susceptible. Under Fe deficient condition, KAN showed delayed chlorosis, high SPAD values, and low malondialdehyde content compared to PBW, indicative of Fe deficient condition. Comparative shoot transcriptomics revealed increased expression of photosynthetic pathway genes in PBW, further suggesting its sensitivity to Fe fluctuations. Under Fe deficiency, both the cultivars showed distinct molecular re-arrangements such as high expression of genes involved in Fe uptake (including membrane transporters) and its remobilization. Specifically, in KAN these changes lead to high root phytosiderophores (PS) biosynthesis and its release, resulting in enhanced Fe translocation index. Utilizing the non-transgenic TILLING (Targeting Induced Lesions in Genomes) technology, we identified TaZIFL4.2D as a putative PS efflux transporter. Characterization of the wheat TILLING lines indicated that TaZIFL4.2 functions in PS release and Fe acquisition, thereby imparting tolerance to Fe deficiency. Altogether, this work highlights the mechanistic insight into Fe deficiency tolerance of hexaploid wheat, thus enabling breeders to select suitable genotypes to utilize nutrients for maximum yields.


Assuntos
Deficiências de Ferro , Triticum , Triticum/metabolismo , Transcriptoma/genética , Ferro/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Raízes de Plantas/metabolismo
9.
Nanomedicine (Lond) ; 19(1): 79-101, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38197372

RESUMO

Tofacitinib is a first-generation JAK inhibitor approved by the US FDA for treating rheumatoid arthritis. It exhibits a broad-spectrum inhibitory effect with abilities to block JAK-STAT signalling. The primary objective of this review is to obtain knowledge about cutting-edge methods for effectively treating a variety of skin problems by including tofacitinib into formulations that are based on nanocarriers. The review also highlights clinical trials and offers an update on published clinical patents. Nanocarriers provide superior performance compared to conventional treatments in terms of efficacy, stability, drug bioavailability, target selectivity and sustained drug release. Current review has the potential to make significant contributions to the ongoing discussion involving dermatological treatments and the prospective impact of nanotechnology on transforming healthcare within this field.


Assuntos
Artrite Reumatoide , Dermatologia , Piperidinas , Pirimidinas , Humanos , Estudos Prospectivos , Artrite Reumatoide/tratamento farmacológico , Sistemas de Liberação de Medicamentos
10.
Cardiol Rev ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189438

RESUMO

Geriatric patients frequently encounter orthostatic hypotension (OH), a multifaceted condition characterized by a significant drop in blood pressure upon assuming an upright position. As the elderly population is particularly susceptible to OH, our review endeavors to comprehensively explore the complex nature of this condition and various factors contributing to its development. We investigate the impact of comorbidities, polypharmacy, age-related physiological changes, and autonomic dysfunction in the pathogenesis of OH. Geriatric patients with OH are faced with an elevated risk of falls, syncope, a decline in their overall quality of life, and hence increased mortality. These implications require careful consideration, necessitating a thorough examination of therapeutic strategies. We evaluate various pharmaceutical and nonpharmacological therapies, delving into the effectiveness and safety of each approach in managing OH within geriatric populations. We explore the role of pharmacotherapy in alleviating symptoms and mitigating OH-related complications, as well as the potential benefits of volume expansion techniques to augment blood volume and stabilize blood pressure. We place particular emphasis on the significance of lifestyle changes and nonpharmacological interventions in enhancing OH management among the elderly. These interventions encompass dietary modifications, regular physical activity, and postural training, all tailored to the unique needs of the individual patient. To optimize outcomes and ensure patient safety, we underscore the importance of individualized treatment plans that take into account the geriatric patient's overall health status, existing comorbidities, and potential interactions with other medications. This review aims to improve clinical practice and patient outcomes by advocating for early detection, properly tailored management, and targeted interventions to address OH in the elderly population. By raising awareness of OH's prevalence and complexities among healthcare professionals, we hope to foster a comprehensive understanding of OH and contribute to the overall wellness and quality of life of this vulnerable demographic.

11.
Proc (Bayl Univ Med Cent) ; 37(1): 135-141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38173995

RESUMO

Table rounds and bedside rounds are two methods healthcare professionals employ during clinical rounds for patient care and medical education. Bedside rounds involve direct patient engagement and physical examination, thus significantly impacting patient outcomes, such as improving communication and patient satisfaction. Table rounds occur in a conference room without the patient present and involve discussing patient data, which is more effective in fostering structured medical education. Both bedside and table rounds have pros and cons, and healthcare professionals should consider the specific requirements of their patients and medical trainees when deciding which approach to use. This research utilized a comprehensive search to identify relevant resources, such as university website links, as well as a PubMed search using relevant keywords such as 'bedside rounding,' 'table rounding,' and 'patient satisfaction.' Relevance, publication date, and study design were the basis for inclusion criteria. This study compared the effectiveness of these two methods based on physician communication, medical education, patient care, and patient satisfaction.

12.
Proc (Bayl Univ Med Cent) ; 37(1): 118-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38174000

RESUMO

Protein supplements are widely consumed by athletes as well as young adults and teenagers going to the gym and are an excellent source to increase protein intake, build muscle mass, and enhance recovery. They are available in the form of powders, gummies, protein bars, and ready-to-drink shakes and have been shown to have effects on almost every system in the body. Subjects consuming whey protein-based supplements regularly show significantly lower systolic blood pressure, while subjects who consume soy-based protein supplements have been reported to show a significant decrease in their systolic and diastolic blood pressures. Favorable effects of soy protein consumption have been observed on the serum lipid profile, with significant decreases in serum low-density lipoprotein and triglyceride levels. Lower postprandial glucose levels have been observed in diabetic subjects as well, which can be attributed to the lower glycemic index of these supplements. This can lead to an indirect decrease in diabetes-related complications. While these supplements affect the body positively, caution has to be exercised while consuming them in excess, as they have been shown to cause hyperfiltration and increased urinary calcium excretion which can, in turn, lead to chronic kidney disease development. This article focuses on the effects of protein supplementation on the human body, with emphasis on the cardiovascular, endocrine, and renal systems.

13.
Drug Deliv Transl Res ; 14(3): 730-756, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37768530

RESUMO

Raloxifene (RLX) is popularly indicated in treatment of osteoporosis and prevention of breast cancer. Owing to its poor aqueous solubility, high pre-systemic metabolism, intestinal glucuronidation, and P-glycoprotein (P-gp) efflux, however, it demonstrates low (< 2%) and inconsistent oral bioavailability. The current work, Quality by Design (QbD)-driven development of phospholipid-embedded nanostructured lipidic carriers (NLCs) of RLX, accordingly, was undertaken to potentiate its lymphatic uptake, augment oral bioavailability, and possibly reduce drug dosage. Factor screening and failure mode effect analysis (FMEA) studies were performed to delineate high-risk factors using solid lipid (glyceryl monostearate), liquid lipid (vitamin E), and surfactant (Tween 80). Response surface optimization studies were performed employing the Box-Behnken design. Mathematical and graphical methods were adopted to embark upon the selection of optimized NLCs with various critical quality attributes (CQAs) of mean particle size as 186 nm, zeta potential of - 23.6 mV, entrapment efficiency of 80.09%, and cumulative drug release at 12 h of 83.87%. The DSC and FTIR studies, conducted on optimized NLCs, indicated successful entrapment of drug into the lipid matrix. In vitro drug release studies demonstrated Fickian diffusion mechanism. In vivo pharmacokinetic studies in rats construed significant improvement in AUC0-72 h (4.48-folds) and in Cmax (5.11-folds), unequivocally indicating markedly superior (p < 0.001) oral bioavailability of RLX-NLCs vis-à-vis marketed tablet formulation. Subsequently, level "A" in vitro/in vivo correlation (IVIVC) was also successfully attempted between the percentages of in vitro drug dissolved and of in vivo drug absorbed at the matching time points. In vitro cytotoxicity and cellular uptake studies also corroborated higher efficacy and successful localization of coumarin-6-loaded NLCs into MG-63 cells through microfluidic channels.


Assuntos
Nanoestruturas , Fosfolipídeos , Ratos , Animais , Portadores de Fármacos , Cloridrato de Raloxifeno , Liberação Controlada de Fármacos , Administração Oral , Tamanho da Partícula , Disponibilidade Biológica
14.
Clin Med (Lond) ; 23(6): 633-634, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38065601

RESUMO

We present a case of a young man with symmetrical peripheral gangrene (SPG) resulting from Streptococcus viridans-related infective endocarditis, an association which has not previously been reported. SPG is associated with up to 40% mortality and may necessitate amputation; early identification and treatment of the precipitating factors is very important.


Assuntos
Endocardite Bacteriana , Endocardite , Masculino , Humanos , Gangrena/etiologia , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico
15.
Sci Rep ; 13(1): 21681, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38066008

RESUMO

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.


Assuntos
Artrite , Etodolac , Humanos , Sistemas de Liberação de Medicamentos/métodos , Pele/metabolismo , Absorção Cutânea , Artrite/tratamento farmacológico , Artrite/metabolismo , Tamanho da Partícula , Administração Cutânea
16.
Infect Immun ; 91(12): e0031123, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37909750

RESUMO

Pulmonary host defense is critical for the control of lung infection and inflammation. An increased expression and activity of Toll-like receptor 4 (TLR4) induce phagocytic uptake/clearance and inflammation against Gram-negative bacteria. In this study, we addressed the mechanistic aspect of the immunomodulatory activity of the TLR4-interacting SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) against Escherichia coli. Binding of the SPA4 peptide to bacteria and direct anti-bacterial effects were investigated using flow cytometric, microscopic, and bacteriological methods. The bacterial uptake and inflammatory cytokine response were studied in dendritic cells expressing endogenous basal level of TLR4 or overexpressing TLR4. The subcellular distribution and co-localization of TLR4 and bacteria were investigated by immunocytochemistry. Furthermore, we studied the cellular expression and co-localization of endoplasmic reticulum (ER) molecules (calnexin and ER membrane protein complex subunit 1; EMC1) with lysosomal-associated membrane protein 1 (LAMP1) in cells infected with E. coli and treated with the SPA4 peptide. Simultaneously, the expression of histone H2A protein was quantitated by immunoblotting. Our results demonstrate no binding or direct killing of the bacteria by SPA4 peptide. Instead, it induces the uptake and localization of E. coli in the phagolysosomes for lysis and simultaneously suppresses the secreted levels of TNF-α. Overexpression of TLR4 further augments the pro-phagocytic and anti-inflammatory activity of SPA4 peptide. A time-dependent change in subcellular distribution of TLR4 and an increased co-localization of TLR4 with E. coli in SPA4 peptide-treated cells suggest an enhanced recognition and internalization of bacteria in conjugation with TLR4. Furthermore, an increased co-localization of calnexin and EMC1 with LAMP1 indicates the involvement of ER in pro-phagocytic activity of SPA4 peptide. Simultaneous reduction in secreted amounts of TNF-α coincides with suppressed histone H2A protein expression in the SPA4 peptide-treated cells. These results provide initial insights into the plausible role of ER and histones in the TLR4-immunomodulatory activity of SPA4 peptide against Gram-negative bacteria.


Assuntos
Escherichia coli , Receptor 4 Toll-Like , Humanos , Receptor 4 Toll-Like/metabolismo , Escherichia coli/metabolismo , Histonas , Fator de Necrose Tumoral alfa/metabolismo , Calnexina/metabolismo , Inflamação/metabolismo , Retículo Endoplasmático/metabolismo , Lipopolissacarídeos/farmacologia
17.
J Antimicrob Chemother ; 78(Suppl 2): ii12-ii17, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995356

RESUMO

BACKGROUND: COVID-19 therapeutics including antiviral and monoclonal antibody treatments (hereafter 'COVID-19 treatments') require rapid administration to be effective. As part of the community-based antiviral and therapeutic treatment pathway for COVID-19 there has been a move from PCR testing in those eligible to a rapid antigen lateral flow testing regime. OBJECTIVES: To determine whether a multi-day lateral flow device (LFD) testing regime is a feasible alternative to PCR for diagnosing symptomatic patients eligible for COVID-19 treatments. An LFD regime might return a positive result more quickly than a PCR and hence expedite access to COVID-19 treatments. METHODS: A retrospective analysis was conducted of diagnostic testing for SARS-CoV-2 with a combination of PCR and LFDs of symptomatic patients eligible for COVID-19 treatments. LFD testing patterns were not assigned. Patients self-censored and the patterns were retro-fitted to the observed results. RESULTS: The LFD testing patterns offered high sensitivity, close to 92%; however, the false positive rate also increased, with most of the multi-day testing patterns having a false positive rate greater than 3%. The highest sensitivity was seen among patients who tested with LFD on the same day as PCR. CONCLUSIONS: There were multiple observed testing behaviours. We conclude that multi-day LFD testing for COVID-19 provides a feasible alternative to PCR to in eligible patients, allowing swift prescription of COVID-19 treatments in most cases. This approach requires acceptance of a trade-off for a small increase in false-positive and -negative results.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Teste para COVID-19 , Estudos Retrospectivos , Antivirais/uso terapêutico , Sensibilidade e Especificidade
18.
Heliyon ; 9(10): e20470, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37860516

RESUMO

Diazotrophic cyanobacteria are known to influence nutrient availability in soil, however, their benefits under elevated CO2 environment, particularly on fruit quality attributes, is a less investigated aspect. Laboratory developed cyanobacterium-fungal biofilm (An-Tr), composed of Anabaena torulosa (An) as the matrix with the partner as Trichoderma viride (Tr), along with the individual partners were evaluated under ambient (aCO2-400 ± 50 ppm) and elevated (eCO2-700 ± 50 ppm) conditions, with and without tomato plants. An-Tr inoculation exhibited distinct and significantly higher values for most of the soil microbiological parameters, plant growth attributes and antioxidant/defense enzyme activities measured at 30 and 60 DAI (days after inoculation). Significant enhancement in soil nutrient availability, leaf chlorophyll, with 45-50% increase in the enzyme activities related to carbon and nitrogen assimilation, higher yields and better-quality parameters of tomato, with An-Tr biofilm or An inoculation, were recorded, particularly under eCO2 conditions. The fruits from An-Tr treatments under eCO2 exhibited a higher titrable acidity, along with more ascorbic acid, carotenoids and lycopene content, highlighting the superiority of this inoculant. Multivariate analyses revealed significant (p ≤ 0.05) interactions among cultures, DAI, and CO2 levels, illustrating that cyanobacterial inoculation can be advocated as a strategy to gainfully sequester eCO2. Significant improvement in yield and fruit quality along with 50% N savings, further attest to the promise of cyanobacterial inoculants for tomato crop in the climate change scenario.

19.
Front Plant Sci ; 14: 1232800, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692444

RESUMO

High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit abscission, thereby causing a significant reduction in yield. To unravel the intricate genetic mechanisms governing heat tolerance in hot pepper, an F2 population was developed through the crossing of two distinct genotypes exhibiting contrasting heat tolerance characteristics: DLS-161-1 (heat tolerant) and DChBL-240 (heat susceptible). The F2 population, along with the parental lines, was subjected to comprehensive phenotyping encompassing diverse morphological, physiological, and biochemical heat-related traits under high temperature conditions (with maximum temperature ranging from 31 to 46.5°C and minimum temperature from 15.4 to 30.5°C). Leveraging the Illumina Nova Seq-6000 platform, Double digest restriction-site associated DNA sequencing (ddRAD-seq) was employed to generate 67.215 Gb data, with subsequent alignment of 218.93 million processed reads against the reference genome of Capsicum annuum. Subsequent variant calling and ordering resulted in 5806 polymorphic SNP markers grouped into 12 LGs. Further QTL analysis identified 64 QTLs with LOD values ranging from 2.517 to 11.170 and explained phenotypic variance ranging from 4.05 to 19.39%. Among them, 21 QTLs, explaining more than 10% phenotypic variance, were identified as major QTLs controlling 9 morphological, 3 physiological, and 2 biochemical traits. Interestingly, several QTLs governing distinct parameters were found to be colocalized, suggesting either a profound correlation between the QTLs regulating these traits or their significant genomic proximity. In addition to the QTLs, we also identified 368380 SSR loci within the identified QTL regions, dinucleotides being the most abundant type (211,381). These findings provide valuable insights into the genetics of heat tolerance in hot peppers. The identified QTLs and SSR markers offer opportunities to develop heat-tolerant varieties, ensuring better crop performance under high-temperature conditions.

20.
Cardiol Rev ; 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37363999

RESUMO

Red meat is the muscle meat of mammals like beef, lamb, and pork that is red due to the abundance of myoglobin pigment and becomes even darker when cooked. The global average per capita consumption of meat and the total amount of meat consumed is rising, and there has been a particularly marked increase in the global consumption of chicken and pork. The consumption of red meat has always been a contentious issue, with data suggesting benefits in terms of nutritional value and at the same time linking its consumption to major health disorders such as endocrine abnormalities, gastrointestinal issues, cancers, and cardiovascular diseases (CVDs). Despite being normalized by major food franchises, red meat consumption may lead to adverse cardiovascular outcomes such as atherosclerosis, ischemic heart disease, stroke, and cardiac failure. Given the evidence that indicates the consumption of red and processed meat as a risk factor for cardiovascular diseases and all-cause mortality, it is important to review the effects of red meat on the risk of cardiovascular diseases.

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