ABSTRACT
Gastrointestinal stromal tumors (GISTs) are the mesenchymal tumors of the gastrointestinal tract. Extra Gastrointestinal stromal tumors (EGISTs) are rare neoplasms that occur outside the gastrointestinal tract [1]. Miettinen et al. [2] described the first EGIST in 1999. EGIST accounts for 10% of all GISTs [3]. The main distinction between GIST and EGIST is the site of origin of the primary tumor, as GIST occurs throughout the GI tract, from the esophagus to the anus, whereas EGIST is a tumor without any connection with the intestinal wall and are reported in the retroperitoneum, mesentery, and omentum [4]. Hu et al. [5] reported a first case report of EGIST of larynx.We present a second case report of Extra-gastrointestinal stromal tumor of larynx a 47-year-old male reported to ENT Department Command Hospital Central Command Lucknow with complaints of Hoarseness. On examination found to have right vocal cord growth for which he underwent excision of right vocal cord growth. Histopathological examination showed typical of a spindle-cell GIST, showing strong immunoreactivity for CD 117, DOG1, Vimentin and CD 99. 6 months follow up post surgery with no recurrence.
ABSTRACT
A distal femoral cemented modular prosthesis is a viable option for post-bone tumor and limb salvage procedures. The major reasons for implant failures are the poor quality of implants, mechanical stress, biochemical reactions, and extended period of the implant in vivo use. Rare incidences have been reported of distal femur prosthesis implant malfunctioning in a subject having osteosarcoma. Common adverse events associated with implant failure include surgical site infections, swelling, pain, revision of the surgical procedure, cyst formation, and build-up of metal debris on soft tissues. Our case report summarizes gross malfunctioning of a distal femur cemented modular prosthesis experienced by a 24-year-old post-operated osteosarcoma patient who developed excruciating sudden pain and the inability to bear weight on the right leg, with the sudden onset of these symptoms developing while turning in bed.
ABSTRACT
This study examines the influence of planting mixture variations on the quality of the percolated water of the rain garden with and without plants. Six planting mixtures in experimental rain gardens have been used. It has been noted that pollutant removal efficiency of RG can exhibit variations based on specific parameters. Notably, RG6, utilizing a planting mix of 75% topsoil and 25% compost, demonstrated the highest performance. These results draw attention to the critical role of the specific planting mixtures in influencing the performance of vital parameters related to pollutant removal. The observation shows that RG5 exhibits exceptional removal efficiency in pH, Total Suspended Solids (TSS), Biological Oxygen Demand (BOD), and Chemical Oxygen Demand (COD), and RG6 performs best in electrical conductivity (EC), Total Dissolved Solids (TDS), Total Nitrogen (TN), and Total Phosphorus (TP) removal. In particular, when analyzing pollutant removal on a surface with Madagascar periwinkle plants, RG6 emerges as the most effective, achieving an impressive efficiency of approximately 49%. For the bare surface, pollutant removal efficiency is 40%. The study outcome will be useful in deciding the composition of the planting mixture, which will keep the rain garden to improve quality and quantitatively hydrological performance, lowering urban flooding magnitude.
Subject(s)
Rain , Phosphorus , Water Pollutants, Chemical , Nitrogen , Biological Oxygen Demand Analysis , Soil/chemistryABSTRACT
Diabetic encephalopathy (DE), a significant micro-complication of diabetes, manifests as neurochemical, structural, behavioral, and cognitive alterations. This condition is especially dangerous for the elderly because aging raises the risk of neurodegenerative disorders and cognitive impairment, both of which can be made worse by diabetes. Despite its severity, diagnosis of this disease is challenging, and there is a paucity of information on its pathogenesis. The pivotal roles of various cellular pathways, activated or influenced by hyperglycemia, insulin sensitivity, amyloid accumulation, tau hyperphosphorylation, brain vasculopathy, neuroinflammation, and oxidative stress, are widely recognized for contributing to the potential causes of diabetic encephalopathy. We also reviewed current pharmacological strategies for DE encompassing a comprehensive approach targeting metabolic dysregulations and neurological manifestations. Antioxidant-based therapies hold promise in mitigating oxidative stress-induced neuronal damage, while anti-diabetic drugs offer neuroprotective effects through diverse mechanisms, including modulation of insulin signaling pathways and neuroinflammation. Additionally, tissue engineering and nanomedicine-based approaches present innovative strategies for targeted drug delivery and regenerative therapies for DE. Despite significant progress, challenges remain in translating these therapeutic interventions into clinical practice, including long-term safety, scalability, and regulatory approval. Further research is warranted to optimize these approaches and address remaining gaps in the management of DE and associated neurodegenerative disorders.
ABSTRACT
An efficient visible-light-induced synthesis of vinyl sulfones has been accomplished via decarboxylative sulfonylation of cinnamic acids using sulfonylazides, p-toluenesulfonylmethyl isocyanide, and ß-keto sulfones as sulfonyl source, in the presence of inexpensive organic photocatalysts like rhodamine B and eosin Y. The reaction is facile, straightforward, and endowed with wide substrate scope and functional group tolerability.
ABSTRACT
In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h-1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min-1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h-1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc-1) and fuel consumption (3 l h-1) were 96%, 7.9 mm, 1230 g cc-1 and 3.0 l h-1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.
Subject(s)
Triticum , Agriculture/methods , Equipment Design , Soil/chemistry , Crop Production/methodsABSTRACT
Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aß) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aß drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aß plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease.
ABSTRACT
The present study is carried out in 42 sampling sites for the measurement of background gamma dose rate in six tehsils of the Bageshwar district that comes under the Kumaun Himalaya, Uttarakhand. The annual effective dose in the pre-monsoon and post-monsoon seasons was estimated from the measured values of the Gamma dose rate. It is found that the minimum and maximum values ranged between 0.01-0.39 mSv per y (Arithmetic Mean = 0.19 mSv per y) in the pre-monsoon and 0.11-0.42 mSv per y (Arithmetic Mean = 0.20 mSv per y) in the post-monsoon season of the year. The finding of the present study shows that the annual effective dose equivalent is higher than the worldwide average value recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation.
Subject(s)
Gamma Rays , Radiation Dosage , Radiation Monitoring , Seasons , Soil Pollutants, Radioactive , India , Radiation Monitoring/methods , Humans , Soil Pollutants, Radioactive/analysis , Background RadiationABSTRACT
The goal of the current study was to create and assess the effectiveness of a hand-pulled ergonomically designed flame weeder. The developed weeder was tested in the field at three operating pressures (20, 30 and 40 Psi) and forward speeds (1.00, 1.25 and 1.50 km/h) to study their effects on plant damage, survival rates, weight preservation rates, weed management effectiveness, soil temperatures, and gas and energy consumption. Thereafter, at optimized values of forward speed and operating pressure, a comparative assessment of flame weeding with traditional methods (mechanical and manual weeding) was done in terms of weed control effectiveness, operational time, energy consumption, and cost of operation. Results showed that the optimal performance of the designed flame weeder was achieved when operated at a speed of 1 km/h and an operating pressure of 40 psi. The survival rate, weight preservation rate, weed control efficiency, change in soil temperature, recovery rate, plant damage, gas consumption, and energy consumption were observed to be 27.3 %, 32.5 %, 91.1 %, 40.74 °C, 8.5 %, 2.2 %, 4.05 kg/h, and 2500.24 MJ/ha, respectively, at optimized values of forward speed (1.00 km/h) and operating pressure (40 Psi). The actual field capacity, field efficiency and operating cost of the flame weeder were 0.0755 ha/h, 94.94 %, and 3620.81 â¹/ha, respectively. Hand weeding had the best level of weed control effectiveness, but it was a laborious, time-consuming process. When compared to manual weeding, flame weeding was 50.42 % cheaper and 94.82 % faster.
ABSTRACT
Site-selective C-H bond functionalization of arenes at the para position remains extremely challenging primarily due to its relative inaccessibility from the catalytic site. As a consequence, it is significantly restricted to the limited molecular scaffolds. Herein, we report a method for the para-C-H borylation of aromatic aldimines and benzylamines using commercially available ligands under iridium catalysis. The established method displayed excellent para-selectivity for variously substituted aromatic aldimines, benzylamines and bioactive molecules. Based on the several control experiments, it has been realized that a Lewis acid-base interaction between the nitrogen and boron functionality guides the para selectivity via a steric shield for the aromatic aldimines, where Bpin acts as a transient directing group. However, the steric shield of the in situ generated N-Bpin moiety controlled the overall selectivity for the para borylation of benzylamines.
ABSTRACT
BACKGROUND: Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases. METHODS: The present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level. RESULTS: Three multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses. CONCLUSIONS: Taken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.
Subject(s)
Computational Biology , Epitopes, T-Lymphocyte , Poxviridae , Viral Vaccines , Viral Vaccines/immunology , Poxviridae/immunology , Poxviridae/genetics , Computational Biology/methods , Epitopes, T-Lymphocyte/immunology , DNA-Directed RNA Polymerases/immunology , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/genetics , Models, Molecular , Animals , Humans , Poxviridae Infections/prevention & control , Poxviridae Infections/immunology , Poxviridae Infections/virology , Epitopes, B-Lymphocyte/immunology , Molecular Docking Simulation , ImmunoinformaticsABSTRACT
Background: Behavioral and psychological symptoms of dementia (BPSD) influence dementia care significantly. BPSD can be affected by factors related to the patient's illness and socio-cultural background. Aim: This study aimed to find a relationship between BPSD with patients' socio-demographic and clinical profiles and their caregivers' distress in a tertiary care center. Materials and Methods: In this hospital-based cross-sectional study, the purposive sampling technique was used to select 100 dementia patients. A comprehensive record of socio-demographic and clinical details was made on a self-prepared semi-structured data sheet. The Neuropsychiatric Inventory Questionnaire was the principal tool to find the BPSD and related caregivers' distress. Results: The sample comprised predominantly Hindu (91%) male patients (66%) with Alzheimer's dementia (76%) coming from rural backgrounds (74%) and joint familial systems (96%), with a mean age of 71.77 ± 7.41 years. Patients' main caregivers were their children/children-in-law (65%). The severity of an overall BPSD and its variable individual domains were directly related to the duration of dementia, patients' age, their cognitive decline, and related decline in activities of living, as well as their caregivers' distress. In comparison to Alzheimer's disease patients, those with other dementia types had more impairment in cognitive functions and activities of daily living and they had a higher number and severity of BPSD. Conclusion: The advancing age, increased duration of dementia, and decline in cognition and related activities of daily living of the patients, as well as their caregivers' distress, are important correlates of BPSD. The findings are essential for the better management of dementia patients.
ABSTRACT
The growing demand for agricultural output and limited resources encourage precision applications to generate higher-order output by utilizing minimal inputs of seed, fertilizer, land, and water. An electronically operated planter was developed, considering problems like ground-wheel skidding, field vibration, and the lack of ease in field adjustments of ground-wheel-driven seed-metering plates. The seed-metering plate of each unit of the developed planter is individually driven by a brushless direct current (BLDC) motor, and a BLDC motor-based aspirator is attached for pneumatic suction of seeds. The revolutions per minute (RPM) of the seed-metering plate are controlled by a microcontroller as per the received data relating to RPM from the ground wheel and the current RPM of the seed-metering plate. A feedback loop with proportional integral derivative (PID) control is responsible for reducing the error. Additionally, each row unit is attached to a parallelogram-based depth control system that can provide depth between 0 and 100 mm. The suction pressure in each unit is regulated as per seed type using the RPM control knob of an individual BLDC motor-based aspirator. The row-to-row spacing can be changed from 350 mm to any desired spacing. The cotton variety selected for the study was RCH 659, and the crucial parameters like orifice size, vacuum pressure, and forward speed were optimized in the laboratory with the adoption of a central composite rotatable design. An orifice diameter of 2.947 mm with vacuum pressure of 3.961 kPa and forward speed of 4.261 km/h was found optimal. A quality feed index of 93% with a precision index of 8.01% was observed from laboratory tests under optimized conditions. Quality feed index and precision index values of 88.8 and 12.75%, respectively, were obtained from field tests under optimized conditions.
ABSTRACT
Proliferation of specific nucleotide sequences within the coding and non-coding regions of numerous genes has been implicated in approximately 40 neurodegenerative disorders. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a neurodegenerative disorder, is distinguished by a pathological triad of sensory neuropathy, bilateral vestibular areflexia and cerebellar impairments. It manifests in adults gradually and is autosomal recessive and multi-system ataxia. Predominantly, CANVAS is associated with biallelic AAGGG repeat expansions in intron 2 of the RFC1 gene. Although various motifs have been identified, only a subset induces pathological consequences, by forming stable secondary structures that disrupt gene functions both in vitro and in vivo. The pathogenesis of CANVAS remains a subject of intensive research, yet its precise mechanisms remain elusive. Herein, we aim to comprehensively review the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.
ABSTRACT
Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Epithelial-Mesenchymal Transition , Humans , Animals , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathologyABSTRACT
A new strategy for the synthesis of amides has been developed using sulfur-mediated decarboxylative coupling of cinnamic acids with amines via oxidative cleavage of the CâC bond.
ABSTRACT
BACKGROUND: Tumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers. METHODS: We present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics. RESULTS: In a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide-major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline. CONCLUSIONS: In this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.
Subject(s)
Antigens, Neoplasm , Immunotherapy , Humans , Antigens, Neoplasm/immunology , Immunotherapy/methods , Gene Regulatory NetworksABSTRACT
BACKGROUND: Chickpea is prone to many abiotic stresses such as heat, drought, salinity, etc. which cause severe loss in yield. Tolerance towards these stresses is quantitative in nature and many studies have been done to map the loci influencing these traits in different populations using different markers. This study is an attempt to meta-analyse those reported loci projected over a high-density consensus map to provide a more accurate information on the regions influencing heat, drought, cold and salinity tolerance in chickpea. RESULTS: A meta-analysis of QTL reported to be responsible for tolerance to drought, heat, cold and salinity stress tolerance in chickpeas was done. A total of 1512 QTL responsible for the concerned abiotic stress tolerance were collected from literature, of which 1189 were projected on a chickpea consensus genetic map. The QTL meta-analysis predicted 59 MQTL spread over all 8 chromosomes, responsible for these 4 kinds of abiotic stress tolerance in chickpea. The physical locations of 23 MQTL were validated by various marker-trait associations and genome-wide association studies. Out of these reported MQTL, CaMQAST1.1, CaMQAST4.1, CaMQAST4.4, CaMQAST7.8, and CaMQAST8.2 were suggested to be useful for different breeding approaches as they were responsible for high per cent variance explained (PVE), had small intervals and encompassed a large number of originally reported QTL. Many putative candidate genes that might be responsible for directly or indirectly conferring abiotic stress tolerance were identified in the region covered by 4 major MQTL- CaMQAST1.1, CaMQAST4.4, CaMQAST7.7, and CaMQAST6.4, such as heat shock proteins, auxin and gibberellin response factors, etc. CONCLUSION: The results of this study should be useful for the breeders and researchers to develop new chickpea varieties which are tolerant to drought, heat, cold, and salinity stresses.
Subject(s)
Cicer , Quantitative Trait Loci , Stress, Physiological , Cicer/genetics , Stress, Physiological/genetics , Chromosome Mapping , Droughts , Genome-Wide Association StudyABSTRACT
Nutritive value of five Cenchrus ciliaris (buffel grass) genotypes (IG96-50, IG96-96, IG96-358, IG96-401 and IG96-403) weredetermined. Their sugar contents (>70 mg/g of dry matter) and ensiling potential were evaluated using in vitro batch culture and in vivo studies. Research indicated significant differences (P < 0.05) in the dry matter, organic matter, ether extract, neutral detergent fiber, acid detergent fiber, cellulose and lignin contents of the C. ciliaris genotypes tested. Genotypes also differed (P < 0.05) in total carbohydrates, structural carbohydrates, non-structural carbohydrates and protein fractions. Genotype IG96-96 had the lowest total digestible nutrients, digestible energy and metabolizable energy contents (377.2 g/kg, 6.95 and 5.71 MJ/kg of dry matter, respectively), and net energy values for lactation, maintenance and growth. After 45 days of ensiling, C. ciliaris silages differed (P < 0.05) in dry matter, pH, and lactic acid contents, and their values ranged between 255-339, 4.06-5.17 g/kg of dry matter and 10.8-28.0 g/kg of dry matter, respectively. Maize silage had higher (P < 0.05) Organic Matter (919.5g/kg of dry matter), ether extract (20.4g/kg of dry matter) and hemi-cellulose (272.3 g/kg of dry matter) than IG96-401 and IG96-96 silages. The total carbohydrates and non-structural carbohydrates of maize silage were higher (P < 0.05), while structural carbohydrates were comparable (P < 0.05) with C. ciliaris silages. Sheep on maize silage had (P < 0.05) higher metabolizable energy, lower crude protein, and digestible crude protein intake (g/kg of dry matter) than those on C. ciliaris silage diets. Nitrogen intake and urinary-N excretion were higher (P < 0.05) on genotype IG96-96 silage diet. Overall, this study suggested that certain C. ciliaris genotypes, notably IG96-401 and IG96-96, exhibited nutritive values comparable to maize silage in sheep studies, offering a promising avenue for future exploration as potential alternatives in diversified and sustainable livestock nutrition programs.
Subject(s)
Cenchrus , Genotype , Nutritive Value , Silage , Zea mays , Animals , Silage/analysis , Zea mays/genetics , Zea mays/chemistry , Sheep , Cenchrus/genetics , Cenchrus/metabolism , Animal Nutritional Physiological Phenomena , Female , Animal Feed/analysis , DigestionABSTRACT
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-ß plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3ß, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.