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1.
Mol Cell ; 81(9): 1905-1919.e12, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33852893

RESUMO

Oxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for ATP production. The reliance on each varies across tissues and cell states, and can influence susceptibility to disease. At present, the full set of molecular mechanisms governing the relative expression and balance of these two pathways is unknown. Here, we focus on genes whose loss leads to an increase in OXPHOS activity. Unexpectedly, this class of genes is enriched for components of the pre-mRNA splicing machinery, in particular for subunits of the U1 snRNP. Among them, we show that LUC7L2 represses OXPHOS and promotes glycolysis by multiple mechanisms, including (1) splicing of the glycolytic enzyme PFKM to suppress glycogen synthesis, (2) splicing of the cystine/glutamate antiporter SLC7A11 (xCT) to suppress glutamate oxidation, and (3) secondary repression of mitochondrial respiratory supercomplex formation. Our results connect LUC7L2 expression and, more generally, the U1 snRNP to cellular energy metabolism.


Assuntos
Glicólise , Fosforilação Oxidativa , Precursores de RNA/metabolismo , Splicing de RNA , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Ácido Glutâmico/metabolismo , Glicogênio/metabolismo , Glicólise/genética , Células HEK293 , Células HeLa , Humanos , Células K562 , Mitocôndrias/genética , Mitocôndrias/metabolismo , Oxirredução , Fosfofrutoquinase-1 Muscular/genética , Fosfofrutoquinase-1 Muscular/metabolismo , Precursores de RNA/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Ribonucleoproteína Nuclear Pequena U1/genética
2.
Nature ; 583(7814): 122-126, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32461692

RESUMO

The cellular NADH/NAD+ ratio is fundamental to biochemistry, but the extent to which it reflects versus drives metabolic physiology in vivo is poorly understood. Here we report the in vivo application of Lactobacillus brevis (Lb)NOX1, a bacterial water-forming NADH oxidase, to assess the metabolic consequences of directly lowering the hepatic cytosolic NADH/NAD+ ratio in mice. By combining this genetic tool with metabolomics, we identify circulating α-hydroxybutyrate levels as a robust marker of an elevated hepatic cytosolic NADH/NAD+ ratio, also known as reductive stress. In humans, elevations in circulating α-hydroxybutyrate levels have previously been associated with impaired glucose tolerance2, insulin resistance3 and mitochondrial disease4, and are associated with a common genetic variant in GCKR5, which has previously been associated with many seemingly disparate metabolic traits. Using LbNOX, we demonstrate that NADH reductive stress mediates the effects of GCKR variation on many metabolic traits, including circulating triglyceride levels, glucose tolerance and FGF21 levels. Our work identifies an elevated hepatic NADH/NAD+ ratio as a latent metabolic parameter that is shaped by human genetic variation and contributes causally to key metabolic traits and diseases. Moreover, it underscores the utility of genetic tools such as LbNOX to empower studies of 'causal metabolism'.


Assuntos
Fígado/metabolismo , NAD/metabolismo , Estresse Fisiológico , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Citosol/metabolismo , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/sangue , Variação Genética , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Levilactobacillus brevis/enzimologia , Levilactobacillus brevis/genética , Masculino , Camundongos , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , Oxirredução , Triglicerídeos/sangue
3.
Ann Surg Oncol ; 31(7): 4197-4198, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38615151

RESUMO

BACKGROUND: Up to 41% of intra- and extra-adrenal paragangliomas are linked to germline mutations with autosomal dominant transmission, which necessitates genetic testing for patients and their relatives.1-4 Certain alterations, such as the succinate dehydrogenase (SDH) subunit B gene mutation, are associated with a significant risk of extra-adrenal, malignant, and metastatic disease forms.4-7 This highlights the need for routine genetic counseling and diligent surveillance, as well as surgeon awareness of hereditary paraganglioma-pheochromocytoma syndrome (HPPS). METHODS: We present a multimedia article featuring a step-by-step video of a complex retroperitoneal resection, enriched with perioperative management insights. RESULTS: A 17-year-old female presented with episodes of hypertension, tachycardia, and diffuse diaphoresis. CT revealed a paraaortic mass adjacent to the left renal hilum later confirmed by a SPECT/CT with iodine-123 meta-iodobenzylguanidine.8 Additional imaging with gallium-68 DOTATATE was not performed then due to unknown mutation status. The patient underwent robotic removal of the tumor and adjacent lymph nodes. Pathology confirmed a poorly differentiated paraganglioma with 0/6 lymph node metastases. Genetic tests revealed SDHB gene mutation, indicative of HPPS.9,10 At 12 months, the patient remained disease-free on CT with normalized metanephrines levels and no detectable circulating tumor DNA. Familial screening detected her mother, maternal uncle, and maternal grandfather to be SDHB mutation carriers, although phenotypically silent. CONCLUSIONS: Robotic-assisted resection can be safe and effective for retroperitoneal malignant paragangliomas. However, management extends beyond surgery and requires cascade genetic testing to address familial risks. Because of the high probability of cancer associated with SDHB mutation, lifelong patient surveillance is imperative.


Assuntos
Paraganglioma Extrassuprarrenal , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Adolescente , Paraganglioma Extrassuprarrenal/cirurgia , Paraganglioma Extrassuprarrenal/genética , Paraganglioma Extrassuprarrenal/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/genética , Prognóstico , Feocromocitoma/cirurgia , Feocromocitoma/genética , Feocromocitoma/patologia
4.
Metabolomics ; 20(2): 36, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446263

RESUMO

INTRODUCTION: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging. OBJECTIVE: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality. METHODS: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact. RESULTS: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased. CONCLUSION: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.


Assuntos
Doenças Mitocondriais , Sepse , Choque Séptico , Humanos , Aminoácidos , N-Formilmetionina , Metabolômica , Metionina , Ácido Láctico , Racemetionina
5.
J Natl Compr Canc Netw ; 22(5): 290-298, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-39019054

RESUMO

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Estadiamento de Neoplasias , Oncologia/normas , Oncologia/métodos
6.
Biogerontology ; 25(4): 627-647, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38240923

RESUMO

The influence of chronic diseases on various facets of macrophage cellular senescence is poorly understood. This study evaluated the impact of chronic hyperglycemia on the induction of cellular senescence and subsequent immunosurveillance functions in RAW264.7 macrophages. Macrophages were cultured under normal glucose (NG; 5 mM), high glucose (HG; 20 mM), and very high glucose (VHG; 40 mM) conditions and assessed for markers of cellular senescence. Hyperglycemia induced strong upregulation of SA-ß-gal activity, and loss of PCNA and Lamin B1 gene expression while markers of cell cycle arrest generally decreased. Non-significant changes in SASP-related proteins were observed while ROS levels slightly decreased and mitochondrial membrane potential increased. Protein concentration on the exosome membrane surface and their stability appeared to increase under hyperglycemic conditions. However, when macrophages were exposed to the secretory media (SM) of senescent preadipocytes, a dramatic increase in the levels of all inflammatory proteins was recorded especially in the VHG group that was also accompanied by upregulation of NF-κB and NLRP3 gene expression. SM treatment to hyperglycemic macrophages activated the TLR-2/Myd88 pathway but decreased the expression of scavenger receptors RAGE, CD36, and Olr-1 while CD44 and CXCL16 expression increased. On exposure to LPS, a strong upregulation in NO, ROS, and inflammatory cytokines was observed. Together, these results suggest that primary markers of cellular senescence are aberrantly expressed under chronic hyperglycemic conditions in macrophages with no significant SASP activation. Nonetheless, hyperglycemia strongly deregulates macrophage functions leading to impaired immunosurveillance of senescent cells and aggravation of inflamm-aging. This work provides novel insights into how hyperglycemia-induced dysfunctions can impact the potency of macrophages to manage senescent cell burden in aging tissues.


Assuntos
Senescência Celular , Glucose , Macrófagos , Animais , Senescência Celular/efeitos dos fármacos , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Glucose/metabolismo , Células RAW 264.7 , Hiperglicemia/metabolismo , Hiperglicemia/imunologia , Biomarcadores/metabolismo , Vigilância Imunológica , Espécies Reativas de Oxigênio/metabolismo
7.
Physiol Plant ; 176(5): e14580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39403868

RESUMO

Plant-virus-host interaction is a complex process involving several players. A constant arms race between the hosts and viruses has led to their co-evolution. Reactive oxygen species (ROS) are important signaling molecules that regulate plant growth, development, and stress responses. Barley yellow dwarf virus (BYDV) has a wide host range and infects several plant species such as barley, rice, oats, wheat, etc. A recent study by Tian et al. (2024) has highlighted that the movement protein (MP) of BYDV is involved in manipulation of the host ROS pathway to promote viral multiplication as well as transmission. The findings display the multifaceted role of a viral protein that is otherwise involved in movement. The limited coding ability of viruses is compensated by their proteins having multiple roles in the modulation of several different host molecular pathways. This is one of the key reasons for viruses being successful pathogens despite their limited coding ability.


Assuntos
Doenças das Plantas , Doenças das Plantas/virologia , Luteovirus/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Interações Hospedeiro-Patógeno , Vírus de Plantas/fisiologia , Proteínas do Movimento Viral em Plantas/metabolismo , Proteínas do Movimento Viral em Plantas/genética , Animais , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
8.
Bioorg Med Chem ; 112: 117883, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39180861

RESUMO

Tagging of cell permeable nuclear localization sequence (NLS) with receptor targeting peptide vectors is an attractive strategy for selectively targeted translocation of therapeutic cargoes. The present study aimed at grafting nuclear localization sequence (NLS) onto breast cancer targeting rL-A9 peptide. Molecular docking analysis revealed higher binding affinity of the peptide, DOTA-NLS-rL-A9 (-26.1 kJ/mol) towards HER2 receptor in comparison to DOTA-rL-A9 peptide (-22.2 kJ/mol). Confocal microscopy data suggested significantly enhanced cellular internalization of NLS-tagged peptide. The engineered HER2-selective, DOTA-NLS-rL-A9 peptide scaffold was radiolabeled with Lu-177 for intracellular delivery of the theranostic radionuclide into tumor cells. [177Lu]Lu-DOTA-NLS-rL-A9 exhibited significantly enhanced binding affinity (4.58 ± 1.77 nM) towards human breast carcinoma SKBR3 cells and cellular internalization (85 % at 24 h) compared to its original analog, [177Lu]Lu-DOTA-rL-A9. In vivo biodistribution studies showed consistent retention of [177Lu]Lu-DOTA-NLS-rL-A9 in the tumor with negligible washout of radioactivity (∼4.1 % ID/g at 48 h). Prolonged tumor activity with rapid off-target tissue clearance resulted in significantly high tumor-to-background ratios. The radiopeptide, [177Lu]Lu-DOTA-NLS-rL-A9 thus, being precisely confined into HER2-expressing tumor cells and exhibiting favourable pharmacokinetic features is an efficient candidate for further screening.


Assuntos
Lutécio , Sinais de Localização Nuclear , Radioisótopos , Receptor ErbB-2 , Humanos , Lutécio/química , Receptor ErbB-2/metabolismo , Animais , Sinais de Localização Nuclear/química , Radioisótopos/química , Camundongos , Feminino , Peptídeos/química , Peptídeos/síntese química , Linhagem Celular Tumoral , Neoplasias da Mama/patologia , Simulação de Acoplamento Molecular , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Distribuição Tecidual
9.
J Pept Sci ; 30(9): e3602, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38600778

RESUMO

Targeted therapy of the highest globally incident breast cancer shall resolve the issue of off-target toxicity concurring with augmented killing of specific diseased cells. Thus, the goal of this study was to prepare a peptide-drug conjugate targeting elevated expression of HER2 receptors in breast cancer. Towards this, the rL-A9 peptide was conjugated with the chemotherapeutic drug doxorubicin (DOX) through a N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker. The synthesized peptide-drug conjugate, rL-A9-DOX, was characterized by mass spectrometry. Molecular docking studies, based on binding energy data, suggested a stronger interaction of rL-A9-DOX with the HER2 receptor in comparison to the unconjugated peptide, rL-A9. The cytotoxic effect of the rL-A9-DOX conjugate was observed to be higher in HER2-positive SKOV3 cells compared to HER2-negative MDA-MB-231 cells, indicating selective cell killing. Cellular internalization of the rL-A9-DOX conjugate was evident from the flow cytometry analysis, where a noticeable shift in mean fluorescent intensity (MFI) was observed for the conjugate compared to the control group. This data was further validated by confocal microscopy, where the fluorescent signal ascertained nuclear accumulation of rL-A9-DOX. The present studies highlight the promising potential of rL-A9-DOX for targeted delivery of the drug into a defined group of cancer cells.


Assuntos
Neoplasias da Mama , Doxorrubicina , Peptídeos , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/química , Peptídeos/química , Peptídeos/farmacologia , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Sistemas de Liberação de Medicamentos , Simulação de Acoplamento Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química
10.
Environ Res ; 242: 117795, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043894

RESUMO

The increasing burden of cardiovascular disease (CVD) remains responsible for morbidity and mortality worldwide; their effective diagnostic or treatment methods are of great interest to researchers. The use of NPs and nanocarriers in cardiology has drawn much interest. The present comprehensive review provides deep insights into the use of current and innovative approaches in CVD diagnostics to offer practical ways to utilize nanotechnological interventions and the critical elements in the CVD diagnosis, associated risk factors, and management strategies of patients with chronic CVDs. We proposed a decision tree-based solution by discussing the emerging applications of NPs for the higher number of rules to increase efficiency in treating CVDs. This review-based study explores the screening methods, tests, and toxicity to provide a unique way of creating a multi-parametric feature that includes cutting-edge techniques for identifying cardiovascular problems and their treatments. We discussed the benefits and drawbacks of various NPs in the context of cost, space, time and complexity that have been previously suggested in the literature for the diagnosis of CVDs risk factors. Also, we highlighted the advances in using NPs for targeted and improved drug delivery and discussed the evolution toward the nano-cardiovascular potential for medical science. Finally, we also examined the mixed-based diagnostic approaches crucial for treating cardiovascular disorders, broad applications and the potential future applications of nanotechnology in medical sciences.


Assuntos
Doenças Cardiovasculares , Nanopartículas , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos , Nanotecnologia
11.
Can J Neurol Sci ; 51(1): 126-128, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36847162

RESUMO

The use of home video recordings (HVRs) may aid in the diagnosis of neurological disorders. However, this practice remains underutilized. Through an anonymous survey, we sought to understand the perspectives of healthcare providers regarding the sharing of HVRs alongside referrals for responsive and economical pediatric neurology care. This was timely given COVID-19 has worsened wait times for diagnosis and consequently treatment. Most providers agree that sharing of HVRs improves patient care (93.1%: 67/73) and prevents both additional investigations (67%: 49/73) and hospital admissions (68.5%: 50/73). However, a minority of providers (21.9 %: 16/73) currently share HVRs alongside their referrals.


Assuntos
Doenças do Sistema Nervoso , Neurologia , Criança , Humanos , Doenças do Sistema Nervoso/terapia , Encaminhamento e Consulta , Pessoal de Saúde , Hospitalização
12.
Cell Biochem Funct ; 42(2): e3970, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456500

RESUMO

There is strong evidence that most individuals in the elderly population are characterized by inflamm-aging which refers to a subtle increase in the systemic pro-inflammatory environment and impaired innate immune activation. Although a variety of distinct factors are associated with the progression of inflamm-aging, emerging research is demonstrating a dynamic relationship between the processes of cellular senescence and inflamm-aging. Cellular senescence is a recognized factor governing organismal aging, and through a characteristic secretome, accumulating senescent cells can induce and augment a pro-inflammatory tissue environment that provides a rationale for immune system-independent activation of inflamm-aging and associated diseases. There is also accumulating evidence that inflamm-aging or its components can directly accelerate the development of senescent cells and ultimately senescent cell burden in tissues in a likely vicious inflammatory loop. The present review is intended to describe the emerging senescence-based molecular etiology of inflamm-aging as well as the dynamic reciprocal interactions between inflamm-aging and cellular senescence. Therapeutic interventions concurrently targeting cellular senescence and inflamm-aging are discussed and limitations as well as research opportunities have been deliberated. An effort has been made to provide a rationale for integrating inflamm-aging with cellular senescence both as an underlying cause and therapeutic target for further studies.


Assuntos
Envelhecimento , Senescência Celular , Inflamação , Humanos , Sistema Imunitário
13.
Clin Med Res ; 22(3): 156-159, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39438149

RESUMO

Inferior vena cava (IVC) filters are commonly placed to prevent the development or worsening of pulmonary emboli. They are also inherently thrombogenic. Here we discuss a case of acute IVC filter thrombosis with the unusual presentation of obstructive shock resulting in death. A man, age 70 years, underwent laminectomy for multilevel spinal stenosis. An IVC filter was placed preoperatively for acute calf deep vein thrombosis (DVT). On postoperative day 4 he developed tachycardia, hypotension, and signs of lower extremity arterial insufficiency. No lower extremity swelling was noted. Imaging showed complete IVC occlusion caudal to the IVC filter with extension to bilateral iliofemoral veins. Arterial flow was preserved. Therapeutic heparinization was initiated and urgent percutaneous thrombectomy was performed. However, the patient developed multi-organ failure and died shortly thereafter. This report describes an uncommon etiology of obstructive shock and highlights a potentially life-threatening thrombotic complication associated with IVC filters that clinicians should be vigilant about.


Assuntos
Choque , Filtros de Veia Cava , Trombose Venosa , Humanos , Filtros de Veia Cava/efeitos adversos , Masculino , Idoso , Trombose Venosa/etiologia , Evolução Fatal , Choque/etiologia , Trombectomia/métodos , Trombose/etiologia , Trombose/diagnóstico
14.
Reprod Domest Anim ; 59(9): e14712, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39205468

RESUMO

The objective of the study was to estimate genetic and phenotypic trends for first lactation production and reproduction traits in Murrah buffaloes. The information of pedigree and targeted traits of 640 Murrah buffaloes was collected for the period from 1997 to 2020. The first lactation production traits included first lactation milk yield (FLMY), 305 days first lactation milk yield (305FLMY), first lactation length (FLL), first lactation peak yield (FPY) whereas reproduction traits included first service period (FSP), first calving interval (FCI) and first dry period (FDP). Genetic and phenotypic trends were estimated. Phenotypic trends for FLMY, 305FLMY, FLL and FPY exhibited as 36.96 ± 8.58 kg/year, 31.93 ± 8.34 kg/year, 1.47 ± 0.55 days/year and 0.12 ± 0.02 kg/year, respectively and respective genetic trends exhibited as 3.73 ± 1.67 kg/year, 1.94 ± 0.76 kg/year, -0.15 ± 0.07 days/year and 0.01 ± 0.01 kg/year, respectively. It was revealed that there were significant (p < 0.05) and positive phenotypic trends for all production traits while genetic trends were significant (p < 0.05) for FLMY and 305FLMY traits. The phenotypic trends of studied reproductive traits indicated that only FDP trait significantly (p < 0.01) decreased (1.87 days/year) over time. For FSP and FCI traits, nonsignificant (p > 0.05) genetic and phenotypic trends indicated no change over time. This study highlighted potential challenges in maintaining reproductive efficiency alongside productivity improvements in Murrah buffaloes.


Assuntos
Búfalos , Lactação , Fenótipo , Reprodução , Animais , Búfalos/fisiologia , Búfalos/genética , Feminino , Lactação/genética , Lactação/fisiologia , Reprodução/genética , Reprodução/fisiologia , Leite , Masculino
15.
Reprod Domest Anim ; 59(7): e14675, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005139

RESUMO

The aim of this research was to assess genetic parameters for first lactation production and reproduction traits in Murrah buffaloes by employing additive and maternal effects. Data on pedigree and specific traits of 640 Murrah buffaloes were gathered from 1997 to 2020. These traits encompassed first lactation milk yield (FLMY), 305-day first lactation milk yield (305FLMY), first lactation length (FLL), first lactation peak yield (FPY), first service period (FSP), first calving interval (FCI) and first dry period (FDP). Genetic evaluations employed six univariate animal models, accounting for both direct and maternal effects, facilitated by THRGIBBS1F90 and POSTGIBBSF90 programs. Fixed factors included in the analysis were period of calving, season of calving and age at first calving. The Bayesian estimates for direct heritability, derived from the most suitable model, were as follows: FLMY: 0.28 ± 0.01, 305FLMY: 0.30 ± 0.01, FLL: 0.19 ± 0.01, FPY: 0.18 ± 0.01, FSP: 0.12 ± 0.01, FCI: 0.14 ± 0.01 and FDP: 0.12 ± 0.01. Maternal effects were found significant, ranging from 5% to 10%, in first lactation traits under Model 2 and Model 5. Additionally, positive and significant genetic and phenotypic correlations were observed among the studied traits. In conclusion, selection based on 305-day first lactation milk yield suggests potential for genetic enhancement in Murrah buffaloes, advocating its inclusion in breeding programmes to bolster early performance. Also, consideration of maternal influences is necessary for genetic progress of animals.


Assuntos
Teorema de Bayes , Búfalos , Lactação , Reprodução , Animais , Búfalos/fisiologia , Búfalos/genética , Feminino , Lactação/fisiologia , Reprodução/fisiologia , Reprodução/genética , Leite , Herança Materna , Cruzamento , Masculino
16.
Bioprocess Biosyst Eng ; 47(5): 725-736, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582779

RESUMO

The global energy crisis has spurred a shift from conventional to clean and sustainable energy sources. Biomass derived from microalgae is emerging as an alternative energy source with diverse applications. Despite the numerous advantages of microalgae, large-scale biomass harvesting is not economical and convenient. Self-flocculation is considered an effective phenomenon facilitated by extracting the flocculating substances from microalgae that assist aggregation of algal cells into flocs. A novel cellulose-based bioflocculant has been synthesized from sewage water grown Chlorella sorokiniana and Scenedesmus abundans for harvesting application. The produced bioflocculant amounted to 38.5% and 19.38% of the dry weight of S. abundans and C. sorokiniana, respectively. Analysis via FTIR, XRD, and FESEM-EDX revealed the presence of cellulose hydroxyapatite (HA) in algae-derived cellulose. Harvesting efficiencies of 95.3% and 89.16% were attained for S. abundans and C. sorokiniana, respectively, at a dosage of 0.5 g/L. Furthermore, the bioflocculant was recovered, enabling its reuse with recovery efficiencies of 52% and 10% for S. abundans and C. sorokiniana, respectively. This simple and efficient approach has the potential to replace other harvesting methods, thereby contributing to the economic algal biofuel production.


Assuntos
Celulose , Chlorella , Scenedesmus , Esgotos , Celulose/química , Floculação , Chlorella/química , Chlorella/crescimento & desenvolvimento , Chlorella/metabolismo , Scenedesmus/química , Scenedesmus/crescimento & desenvolvimento , Scenedesmus/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Microscopia Eletrônica de Varredura , Nanoestruturas/química
17.
Bioprocess Biosyst Eng ; 47(9): 1471-1482, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38874619

RESUMO

The present study optimized pre-treatment conditions for bioenzyme-mediated hydro-distillation (BMHD) for extraction of mint oil from mentha leaves and the results were compared with those of traditional hydro-distillation (HD) method using response surface methodology. The bio-enzymes produced from moringa leaves had maximum pectinase activity (287.04 µg of sugar/min/ml) followed by xylanase (87.78 µg of sugar/min/ml) while endoglucanase, exoglucanase and amylase activities were comparatively low. The optimized conditions for HD were 69.08 temperature for 173.70 min with water:sample of 10.0. The optimized conditions for enzyme pre-treatment of mentha leaves by BMHD were enzyme concentration of 8%, for a period of 120 min at an incubation period of 40 â„ƒ. The yield (%) and menthol content (%) of the oil at optimized conditions by HD were 1.55 ml/100 g of sample and 56.40% menthol content, respectively, and for BMHD the yield and menthol content (%) of the oil at optimized conditions were 3.69% and 72.80%, respectively. It was found that BMHD leads to a 130% increase in the yield of mint oil and a 10% increase in menthol content as compared to the HD method. No significant difference in physical parameters was observed in mint oil extracted via both methods. Therefore, BMHD is a cost-effective and sustainable approach having an edge over the HD method without compromising the quality and could be a viable approach for commercial purposes.


Assuntos
Destilação , Mentha , Mentol , Folhas de Planta , Mentha/química , Mentol/química , Folhas de Planta/química , Destilação/métodos , Óleos de Plantas/química
18.
J Labelled Comp Radiopharm ; 67(4): 131-144, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342496

RESUMO

Trastuzumab is a US-FDA-approved humanized monoclonal antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The aim of the present work is to optimize a freeze-dried formulation of DOTA-Trastuzumab conjugate for the preparation of patient doses of [177Lu]Lu-Trastuzumab for radioimmunotherapy of breast cancer. The formulation of [177Lu]Lu-Trastuzumab usually takes a long time, and thus, such a process is not suitable for the routine preparation of this agent in hospital radiopharmacies. To circumvent this, a pre-synthesized DOTA-Trastuzumab conjugate as a freeze-dried formulation is proposed. In the present work, DOTA-Trastuzumab conjugate was subjected to a freeze-drying process after the addition of optimized amounts of radioprotectant and cryoprotectant. [177Lu]Lu-DOTA-Trastuzumab was prepared by incubating the lyophilized powder of the kit vial with medium-specific activity 177LuCl3. The final radiochemical purity of [177Lu]Lu-DOTA-Trastuzumab, prepared using freeze-dried kit, was determined to be >95%. To ascertain the reproducibility of the procedure, six consecutive batches of the freeze-dried formulation were prepared, radiolabeled, and evaluated by carrying out both in vitro and ex vivo studies. The consistency of the results of all the six consecutive batches confirmed the robustness and utility of the in-house optimized freeze-dried formulation for the preparation of patient doses of [177Lu]Lu-Trastuzumab at hospital radiopharmacies.


Assuntos
Neoplasias da Mama , Radioisótopos , Humanos , Feminino , Radioisótopos/uso terapêutico , Trastuzumab , Reprodutibilidade dos Testes , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Mama/radioterapia , Lutécio/uso terapêutico
19.
J Anim Breed Genet ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39175362

RESUMO

The objective of the study was to estimate genetic parameters of the growth traits under Bayesian inference in Harnali sheep. The information of pedigree and targeted traits of 2404 Harnali animals born to 159 sires and 695 dams was collected for the period from 1998 to 2021. The growth traits included weight at birth (BWT), 3 (WWT), 6 (6WT) and 12 (YWT) months of age. The genetic evaluation was carried out using six univariate animal models comprising direct and maternal effects using THRGIBBS1F90 and POSTGIBBSF90 programs. The fixed factors adjusted in the analysis were period of birth, sex of lamb and dam's weight at lambing. Bayesian estimates of direct heritability under best model for BWT, WWT, 6WT and YWT traits were 0.16 ± 0.04, 0.10 ± 0.04, 0.18 ± 0.04, and 0.05 ± 0.03, respectively. The significant maternal influences observed for BWT and WWT traits with 9% and 8% contribution to total phenotypic variances, respectively. Additionally, maternal permanent environmental influences were observed to BWT (4%) and YWT trait (3%). The genetic and phenotypic correlations among studied traits were high and positive. The genetic changes were positive and significant for WWT only. It was concluded that the weight at 6 months of age can be continued as selection criterion for further genetic improvement through selection. Also, maternal effects should be considered in breeding programme for enhancing early growth performance in Harnali sheep.

20.
Drug Dev Res ; 85(1): e22138, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38078492

RESUMO

The continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60% PE. Therefore, duramycin is an attractive candidate for the formulation of probes for in situ visualization of E. coli driven focal infections. The aim of the present study is to develop 99m Tc labeled duramycin as a single-photon emission computed tomography (SPECT)-based agent to image such infections. Duramycin was successfully conjugated with a bifunctional chelator, hydrazinonicotinamide (HYNIC). PE specificity of HYNIC-duramycin was confirmed by a dye release assay on PE-containing model membranes. Radiolabeling of HYNIC-duramycin with 99m Tc was performed with consistently high radiochemical yield (>90%) and radiochemical purity (>90%). [99m Tc]Tc-HYNIC-duramycin retained its specificity for E. coli, in vitro. SPECT and biodistribution studies showed that the tracer could specifically identify E. coli driven infection at 3 h post injection. While 99m Tc-labeled duramycin is employed for monitoring early response to cancer therapy and cardiotoxicity, the current studies have confirmed, for the first time, the potential of utilizing 99m Tc labeled duramycin as an imaging agent for detecting bacteria. Its application in imaging PE-positive bacteria represents a novel and promising advancement.


Assuntos
Bacteriocinas , Escherichia coli , Compostos de Organotecnécio , Compostos de Organotecnécio/química , Distribuição Tecidual , Peptídeos/química , Peptídeos/metabolismo
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