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1.
Artigo em Inglês | MEDLINE | ID: mdl-39356359

RESUMO

INTRODUCTION: Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) refer to a heterogenous group of rare neoplasms which is usually composed of a neuroendocrine population which is either well differentiated and more frequently poorly differentiated along with a non-neuroendocrine component, each of the above accounting for at least 30% of the tumour population. It is most commonly seen in the gastro-entero-pancreatic tract. MiNENs have an aggressive behaviour due to its high grade neuroendocrine component and have poor prognosis. This is the first case reported in literature of a MiNEN in the oropharynx. CASE REPORT: 69 year old male patient with no co morbidities presented to the outpatient department with complains of odynophagia for 1 month. He had history of neoadjuvant chemotherapy followed by transoral robotic surgery (TORS) with right selective neck dissection (SND) done in 2019 for carcinoma base of tongue. On flexible laryngoscopy, an ulcerative lesion was noted over the left base of tongue. Although PET scan done showed no significant abnormalities. Biopsy from the lesion showed features of poorly differentiated carcinoma along with morphological features of poorly differentiated neuroendocrine carcinoma (small cell carcinoma). He was planned for upfront surgery (TORS with left SND). Post operatively recovery was uneventful and patient was on ryles tube feed for 12 days. Final histopathology report showed features of mixed neuroendocrine non neuroendocrine neoplasm. He has been on follow up for 1 year with no features of recurrence. CONCLUSION: MiNEN is an aggressive tumour which has poor prognosis and is most commonly located in the gastrointestinal tract. This is the first case reported in oropharynx who has been successfully treated and has been on follow up.

2.
Heliyon ; 10(19): e38639, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39397960

RESUMO

Short-duration and early-bulking potato varieties are well-suited for commercial cultivation in the subtropical Indo-Gangetic plains of India. To maximize seed tuber yield, prevent late-season exposure to aphid vectors, and facilitate the timely planting of wheat crops during the rabi season, it is essential to cut the haulms (vines) of seed potatoes at the earliest possible time. A study was conducted to standardize the optimal vine-killing date for two popular potato varieties in the north-western plains of India, Kufri Pukhraj and Kufri Jyoti, by examining variations in seed yield across different vine-killing dates and assessing the incidence of aphid vectors transmitting potato viruses. Tubers were planted on 15 October for two consecutive seasons, and haulms were cut at 70, 80, and 90 days after planting (DAP), with continuous monitoring of aphid populations. Results showed that total tuber yield and tuber numbers increased with delayed vine-killing. Similarly, the yield and number of oversized tubers significantly rose as the vine-killing date was extended. However, seed-size and undersized tuber yields were largely unaffected, while the number of undersized tubers decreased between 70 and 90 DAP. Further, the gain in total tuber yield and yield of over-sized tubers occurred mainly during 70-80 DAP for Kufri Pukhraj in contrast to Kufri Jyoti where maximum increase occurred between 80 and 90 DAP. Therefore, it is concluded that the optimum time of vine killing for maximum seed tuber yield is directly linked to the tuber growth cycle of individual variety. The period of maximum incidence of aphid vectors varied between the two years. Based on the incidence of Myzus persicae, the seed crops in north-western plains of India should not be extended beyond last week of December although real time monitoring of the aphid incidence is recommended.

3.
Cureus ; 16(8): e67818, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39323715

RESUMO

INTRODUCTION: Vitamin D, beyond bone metabolism, has played a significant role in various physiological processes, including modulation of oxidative stress and maintenance of vascular architecture. Oxidative stress, a state of altered balance between reactive oxygen species (ROS) and antioxidants, is a critical factor in the pathogenesis of various chronic diseases. Our study aims to explore the intricate relationship between serum vitamin D levels and markers of oxidative stress in normotensive and hypertensive individuals. MATERIALS AND METHODS: A total of 108 age-matched participants (35 to 50 years) of both genders (54 males and 54 females) were included in this cross-sectional study according to the study design and assessed for their serum vitamin D level by using enzyme-linked immunosorbent assay (ELISA) method and serum malondialdehyde (MDA) level by using a spectrophotometer at 540 nm after measurement of the blood pressure. The data were entered in a Microsoft Excel sheet and analyzed using Statistical Package for Social Science (SPSS) software version 20. RESULTS: Our findings demonstrate a significant inverse correlation between serum vitamin D levels and MDA (r = -0.71, p < 0.001), indicating lower lipid peroxidation with higher vitamin D levels. Our study concludes by evident higher serum vitamin D levels associated with reduced oxidative stress, reflected by lower MDA. CONCLUSION: These findings suggest a potential protective role of vitamin D against oxidative damage, which could have implications for the prevention of oxidative stress-related diseases.

4.
Protein J ; 43(5): 967-982, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39306651

RESUMO

Cationic amino acid binding protein (CLasArgBP), one of the two amino acid binding receptor in Candidatus Liberibacter asiaticus (CLas), is predominately expressed in citrus psyllids as a part of ATP-binding cassette transport system. The present study describes characterization of CLasArgBP by various biophysical techniques and in silico study, to identify potential inhibitor molecules against CLasArgBP through virtual screening and MD simulations. Further, in planta study was carried out to assess the effect of selected inhibitors on Huanglongbing infected Mosambi plants. The results showed that CLasArgBP exhibits pronounced specificity for arginine, histidine and lysine. Surface plasmon resonance (SPR) study reports highest binding affinity for arginine (Kd, 0.14 µM), compared to histidine and lysine (Kd, 15 µΜ and 26 µΜ, respectively). Likewise, Differential Scanning Calorimetry (DSC) study showed higher stability of CLasArgBP for arginine, compared to histidine and lysine. N(omega)-nitro-L-arginine, Gamma-hydroxy-L-arginine and Gigartinine emerged as lead compounds through in silico study displaying higher binding energy and stability compared to arginine. SPR reports elevated binding affinities for N(omega)-nitro-L-arginine and Gamma-hydroxy-L-arginine (Kd, 0.038 µΜ and 0.061 µΜ, respectively) relative to arginine. DSC studies showed enhanced thermal stability for CLasArgBP in complex with selected inhibitors. Circular dichroism and fluorescence studies showed pronounced conformational changes in CLasArgBP with selected inhibitors than with arginine. In planta study demonstrated a substantial decrease in CLas titer in treated plants as compared to control plants. Overall, the study provides the first comprehensive characterization of cationic amino acid binding protein from CLas, as a potential drug target to manage HLB disease.


Assuntos
Proteínas de Bactérias , Proteínas de Bactérias/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Rhizobiaceae/química , Rhizobiaceae/metabolismo , Simulação de Dinâmica Molecular , Doenças das Plantas/microbiologia , Arginina/química , Arginina/metabolismo , Citrus/química , Citrus/microbiologia , Liberibacter/química , Liberibacter/metabolismo
5.
Sci Rep ; 14(1): 21596, 2024 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285183

RESUMO

In the realm of disease vectors and agricultural pest management, insecticides play a crucial role in preserving global health and ensuring food security. The pervasive use, particularly of organophosphates (OPs), has given rise to a substantial challenge in the form of insecticide resistance. Carboxylesterases emerge as key contributors to OP resistance, owing to their ability to sequester or hydrolyze these chemicals. Consequently, carboxylesterase enzymes become attractive targets for the development of novel insecticides. Inhibiting these enzymes holds the potential to restore the efficacy of OPs against which resistance has developed. This study aimed to screen the FooDB library to identify potent inhibitory compounds targeting carboxylesterase, Ha006a from the agricultural pest Helicoverpa armigera. The ultimate objective is to develop effective interventions for pest control. The compounds with the highest scores underwent evaluation through docking studies and pharmacophore analysis. Among them, four phytochemicals-donepezil, protopine, 3',4',5,7-tetramethoxyflavone, and piperine-demonstrated favorable binding affinity. The Ha006a-ligand complexes were subsequently validated through molecular dynamics simulations. Biochemical analysis, encompassing determination of IC50 values, complemented by analysis of thermostability through Differential Scanning Calorimetry and interaction kinetics through Isothermal Titration Calorimetry was conducted. This study comprehensively characterizes Ha006a-ligand complexes through bioinformatics, biochemical, and biophysical methods. This investigation highlights 3',4',5,7-tetramethoxyflavone as the most effective inhibitor, suggesting its potential for synergistic testing with OPs. Consequently, these inhibitors offer a promising solution to OP resistance and address environmental concerns associated with excessive insecticide usage, enabling a significant reduction in their overuse.


Assuntos
Carboxilesterase , Inseticidas , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Animais , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/metabolismo , Carboxilesterase/química , Inseticidas/farmacologia , Inseticidas/química , Simulação de Dinâmica Molecular , Mariposas/enzimologia , Mariposas/efeitos dos fármacos , Controle de Pragas/métodos , Resistência a Inseticidas , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Helicoverpa armigera
6.
Ther Deliv ; 15(9): 717-735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39259258

RESUMO

Apigenin, a potent natural flavonoid, has emerged as a key therapeutic agent due to its multifaceted medicinal properties in combating various diseases. However, apigenin's clinical utility is greatly limited by its poor water solubility, low bioavailability and stability issues. To address these challenges, this review paper explores the innovative field of nanotechnology-based delivery systems, which have shown significant promise in improving the delivery and effectiveness of apigenin. This paper also explores the synergistic potential of co-delivering apigenin with conventional therapeutic agents. Despite the advantageous properties of these nanoformulations, critical challenges such as scalable production, regulatory approvals and comprehensive long-term safety assessments remain key hurdles in their clinical adoption which must be addressed for commercialization of apigenin-based formulations.


Apigenin is a natural substance found in plants that might help treat illnesses like cancer, diabetes, heart problems and brain disorders. But it doesn't work very well because it doesn't dissolve in water, is hard for the body to use and isn't very stable. To fix this, scientists are putting apigenin inside tiny carriers called nanocarriers. These tiny carriers help apigenin dissolve better, be absorbed by the body more easily and work better.There are different kinds of nanocarriers, like tiny fat bubbles, tiny solid particles and tiny gels. These can be made to target specific parts of the body, which helps reduce side effects. Apigenin can also be mixed with other medicines in these carriers to work even better.However, there are big challenges in making these treatments widely available, like making enough of them, getting permission from health authorities and making sure they are safe for a long time. This review talks about the latest progress and future possibilities in using nanotechnology to deliver apigenin, aiming to make it better for treating diseases.


Assuntos
Apigenina , Apigenina/administração & dosagem , Apigenina/química , Apigenina/farmacocinética , Apigenina/farmacologia , Humanos , Animais , Disponibilidade Biológica , Solubilidade , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Nanotecnologia/métodos , Sistemas de Liberação de Fármacos por Nanopartículas/química
7.
Indian J Otolaryngol Head Neck Surg ; 76(4): 3566-3569, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39130238

RESUMO

Cervical lymph node metastasis is one of the most common clinical presentations of papillary thyroid carcinoma (PTC). Occult thyroid carcinoma is described as absence of primary tumour or with presence of microcarcinoma in thyroid with cervical lymph node metastasis. Frequency of occult thyroid cancer has decreased due to developments in imaging and improved accuracy of histological examinations. 38 year old male presented to us with complaints of swelling over the left side of neck for the past 2 months. Ultrasonography was suggestive of multiple suspicious enlarged nodes in left level II, III, IV and V and fine needle aspiration cytology showed features of metastatic PTC. He was planned for total thyroidectomy with central compartment clearance and bilateral functional neck dissection. Final histopathology staging was pT0N1b. Radioactive iodine (RAI) screening showed residual functioning thyroid and later therapeutic RAI was administered. He has been on regular follow up and disease free for 1 year post treatment. Occult thyroid carcinoma is a rare diagnosis with multiple treatment plans. Few hypothesis for this entity includes tumor regression, ectopic thyroid carcinoma or missed pathological findings.

8.
Cell Signal ; 122: 111329, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39098704

RESUMO

Mitochondria, traditionally known as cellular powerhouses, now emerge as critical signaling centers influencing cancer progression and drug resistance. The review highlights the role that apoptotic signaling, DNA mutations, mitochondrial dynamics and metabolism play in the development of resistance mechanisms and the advancement of cancer. Targeted approaches are discussed, with an emphasis on managing mitophagy, fusion, and fission of the mitochondria to make resistant cancer cells more susceptible to traditional treatments. Additionally, metabolic reprogramming can be used to effectively target metabolic enzymes such GLUT1, HKII, PDK, and PKM2 in order to avoid resistance mechanisms. Although there are potential possibilities for therapy, the complex structure of mitochondria and their subtle role in tumor development hamper clinical translation. Novel targeted medicines are put forth, providing fresh insights on combating drug resistance in cancer. The study also emphasizes the significance of glutamine metabolism, mitochondrial respiratory complexes, and apoptotic pathways as potential targets to improve treatment effectiveness against drug-resistant cancers. Combining complementary and nanoparticle-based techniques to target mitochondria has demonstrated encouraging results in the treatment of cancer, opening doors to reduce resistance and enable individualized treatment plans catered to the unique characteristics of each patient. Suggesting innovative approaches such as drug repositioning and mitochondrial drug delivery to enhance the efficacy of mitochondria-targeting therapies, presenting a pathway for advancements in cancer treatment. This thorough investigation is a major step forward in the treatment of cancer and has the potential to influence clinical practice and enhance patient outcomes.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Mitocôndrias , Neoplasias , Transdução de Sinais , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Dinâmica Mitocondrial/efeitos dos fármacos
9.
Sci Rep ; 14(1): 19615, 2024 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179653

RESUMO

Electrospinning stands out as a flexible and viable method, presenting designed nanoscale materials with customized properties. This research demonstrates the immobilization of carboxylesterase protein Ha006a, reported for its adequacy in pesticide bioremediation by utilizing the electrospinning strategy. This strategy was utilized to create nanofibers by incorporating variable mixtures of biodegradable and cost-effective polyvinyl alcohol (PVA)-chitosan (CS) nanofiber solution (PVA100, PVA96, PVA94, PVA92 and PVA90). All the mixtures were electrospun at a reliable voltage of 21 kV, maintaining a gap of 12 cm from the nozzle. The Ha006a, sourced from Helicoverpa armigera, was consolidated into the optimized PVA90 polymer mixture. The electrospun nanofibers experienced comprehensive characterization utilizing distinctive microscopy and spectroscopy procedures counting FESEM, TGA, XRD and FTIR. The comparative investigation of the esterase property, ideal parameters and stability of the unbound and bound/immobilized Ha006a was scrutinized. The results uncovered an essential elevation in the ideal conditions of enzyme activity post-immobilization. The PVA-CS control nanofiber and Ha006a-PVA-CS showed a smooth structure, including an average breadth of around 170.5 ± 44.2 and 222.5 ± 66.5 nm, respectively. The enzyme-immobilized nanofibers displayed upgraded stability and comprehensive characterization of the nanofiber, which guaranteed genuineness and reproducibility, contributing to its potential as a potent device for bioremediation applications. This investigation opens the way for the manufacture of pesticide-resistant insect enzyme-based nanofibers, unlocking their potential for assorted applications, counting pesticide remediation and ensuring environmental sustainability.


Assuntos
Carboxilesterase , Quitosana , Estabilidade Enzimática , Enzimas Imobilizadas , Nanofibras , Álcool de Polivinil , Álcool de Polivinil/química , Nanofibras/química , Quitosana/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Carboxilesterase/metabolismo , Carboxilesterase/química , Animais , Concentração de Íons de Hidrogênio
11.
Sci Rep ; 14(1): 17662, 2024 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-39085276

RESUMO

This study focused on strategically employing the carboxylesterase enzyme Ha006a, derived from the pesticide-resistant microorganism Helicoverpa armigera, to detect atrazine. A comprehensive analysis through biochemical, biophysical and bioinformatics approaches was conducted to determine the interaction between the Ha006a protein and the herbicide atrazine. These experimental findings elucidated the potential of leveraging the inherent pesticide sequestration mechanism of the Ha006a enzyme for sensor fabrication. Numerous optimizations were undertaken to ensure the precision, reproducibility and convenient storage of the resulting electrochemical sensor, Ha006a/MCPE. This biosensor exhibited exceptional performance in detecting atrazine, demonstrating outstanding selectivity with a lower limit of detection of 5.4 µM. The developed biosensor has emerged as a reliable and cost-effective green tool for the detection of atrazine from diverse environmental samples. The Ha006a-based biosensor fabrication has expanded the possibilities for the efficient integration of insect enzymes as analytical tools, paving the way for the design of cost-effective biosensors capable of detecting and quantifying pesticides.


Assuntos
Atrazina , Técnicas Biossensoriais , Técnicas Eletroquímicas , Simulação de Acoplamento Molecular , Atrazina/análise , Atrazina/metabolismo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Animais , Herbicidas/análise , Carboxilesterase/metabolismo , Reprodutibilidade dos Testes
12.
Biochem Biophys Res Commun ; 725: 150253, 2024 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880080

RESUMO

Type1 Non-specific Lipid Transfer Protein (CsLTP1) from Citrus sinensis is a small cationic protein possessing a long tunnel-like hydrophobic cavity. CsLTP1 performing membrane trafficking of lipids is a promising candidate for developing a potent drug delivery system. The present work includes in-silico studies and the evaluation of drugs binding to CsLTP1 using biophysical techniques along with the investigation of CsLTP1's ability to enhance the efficacy of drugs employing cell-based bioassays. The in-silico investigations identified Panobinostat, Vorinostat, Cetylpyridinium Chloride, and Fulvestrant with higher affinities and stability of binding to the hydrophobic pocket of CsLTP1. SPR studies revealed strong binding affinities of anticancer drugs, Panobinostat (KD = 1.40 µM) and Vorinostat (KD = 2.17 µM) to CsLTP1 along with the binding and release kinetics. CD and fluorescent spectroscopy revealed drug-induced conformational changes in CsLTP1. CsLTP1-associated drug forms showed remarkably enhanced efficacy in MCF-7 cells, representing increased cell cytotoxicity, intracellular ROS, reduced mitochondrial membrane potential, and up-regulation of proapoptotic markers than the free drugs employing qRT-PCR and western blot analysis. The findings demonstrate that CsLTP1 binds strongly to hydrophobic drugs to facilitate their transport, hence improving their therapeutic efficacy revealed by the in-vitro investigations. This study establishes an excellent foundation for developing CsLTP1-based efficient drug delivery system.


Assuntos
Antineoplásicos , Proteínas de Transporte , Citrus sinensis , Humanos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Células MCF-7 , Citrus sinensis/química , Sistemas de Liberação de Medicamentos/métodos , Simulação de Acoplamento Molecular , Apoptose/efeitos dos fármacos , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Ligação Proteica
13.
Heliyon ; 10(10): e31507, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38831819

RESUMO

Diploid inbred-based F1 hybrid True Potato Seed (DHTPS) breeding is a novel technique to transform potato breeding and cultivation across the globe. Significant efforts are being made to identify elite diploids, dihaploids and develop diploid inbred lines for heterosis exploitation in potatoes. Self-incompatibility is the first obstacle for developing inbred lines in diploid potatoes, which necessitates the introgression of a dominant S locus inhibitor gene (Sli) for switching self-incompatibility to self-compatibility. We evaluated a set of 357 diploid clones in different selfing generations for self-compatibility and degree of homozygosity using Kompetitive Allele Specific PCR (KASP) Single Nucleotide Polymorphism (SNP) markers. A subset of 10 KASP markers of the Sli candidate region on chromosome 12 showed an association with the phenotype for self-compatibility. The results revealed that the selected 10 KASP markers for the Sli gene genotype could be deployed for high throughput rapid screening of self-compatibility in diploid populations and to identify new sources of self-compatibility. The homozygosity assessed through 99 KASP markers distributed across all the chromosomes of the potato genome was 20-78 % in founder diploid clones, while different selfing generations, i.e., S0, S1, S2 and S3 observed 36.1-80.4, 56.9-82.8, 59.5-85.4 and 73.7-87.8 % average homozygosity, respectively. The diploid plants with ∼80 % homozygosity were also observed in the first selfing generation, which inferred that homozygosity assessment in the early generations itself could identify the best plants with high homozygosity to speed up the generation of diploid inbred lines.

14.
Cureus ; 16(5): e61245, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38939274

RESUMO

INTRODUCTION: Hypertension (HTN), a leading risk factor for cardiovascular diseases, is intricately linked with endothelial dysfunction, a hallmark of vascular pathology. The effect of oxidative stress in maintaining the optimum endothelial function in the regulation of blood pressure is yet to be explored. While numerous factors contribute to the pathogenesis of HTN, emerging evidence highlights the pivotal role of oxidative stress in endothelial dysfunction, offering novel insights into the underlying mechanisms. AIM: Our study delves into the multifaceted relationship between oxidative stress and endothelial dysfunction in HTN, elucidating key molecular pathways and potential therapeutic avenues. Our study aims to find out the association between oxidative stress and endothelial function in the regulation of blood pressure. METHODS: A total of 108 age-matched participants of both genders were divided into three groups by following the guidelines of the American Heart Association (AHA) classification for HTN. Blood pressure was recorded manually in resting posture three times at an interval of 10 minutes using a sphygmomanometer after providing 10 minutes of rest before the first reading. Parameters of oxidative stress and endothelial function were measured by using a UV spectrophotometer. Our study results were depicted as mean ± SD. RESULTS: The correlation between our variables was performed using Spearman's correlation considering the value of p<0.05 as statistically significant. Serum malondialdehyde (MDA), a parameter of oxidative stress, was found to be increasing and serum nitric oxide (NO), a parameter to assess endothelial function, was found to be decreasing as the blood pressure increased. These observations are indicative that optimal oxidative stress and optimal endothelial function are required to maintain normal blood pressure regardless of gender. CONCLUSIONS: All persons who are suspected of future cardiovascular risks should be regularly checked for these parameters to avoid cardiovascular morbidity such as HTN.

15.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2895-2901, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883551

RESUMO

Myofibrosarcoma is a distinct mesenchymal malignancy which commonly occurs in head and neck region. It has a high tendency for local recurrence and distant metastasis. 39-year-old male presented with epistaxis, nasal obstruction and left sided complete loss of vision. He underwent functional endoscopic sinus surgery and guided biopsy. MRI scan showed a lesion epicentred in the left maxillary sinus, superiorly extending into the orbit. He underwent Class 4b maxillectomy with neck dissection, tracheostomy and free flap reconstruction. Histopathological examination yielded final diagnosis as myofibrosarcoma of maxilla. The patient was planned for adjuvant radiotherapy and has been disease free for 3 years.

16.
Bioorg Chem ; 149: 107473, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38820940

RESUMO

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.


Assuntos
Antibacterianos , Benzimidazóis , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Sulfonamidas , Benzimidazóis/farmacologia , Benzimidazóis/química , Benzimidazóis/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Estrutura Molecular , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Di-Hidropteroato Sintase/antagonistas & inibidores , Di-Hidropteroato Sintase/metabolismo , Humanos , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Escherichia coli/efeitos dos fármacos
17.
Artigo em Inglês | MEDLINE | ID: mdl-38766821

RESUMO

Neurological disorders present a formidable challenge in healthcare, necessitating the continuous exploration of innovative therapeutic avenues. This review delves into the burgeoning field of natural diterpenoid derivatives and their promising role in addressing neurological disorders. Derived from natural sources, these compounds exhibit a diverse range of pharmacological properties, positioning them as potential agents for treating conditions such as Alzheimer's and Parkinson's disease. The review highlights recent advancements, shedding light on the multifaceted mechanisms through which diterpenoid derivatives exert their effects, from antiinflammatory to neuroprotective actions. As the scientific community navigates the translational journey from bench to bedside, integrating these natural compounds into neurotherapeutics emerges as a compelling prospect. This exploration of the therapeutic frontiers of natural diterpenoid derivatives signifies a significant step towards innovative and effective strategies in the management of neurological disorders. It highlights the potential of natural compounds to revolutionize neurotherapeutics.

18.
J Laparoendosc Adv Surg Tech A ; 34(7): 639-645, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38722056

RESUMO

Introduction: Urologic complications are thought to be the most common surgical complication of renal transplantation. Ureteral pathology, including stenosis, urine leak, and vesicoureteral reflux, predominates. Although endourologic and interventional radiological management may be utilized, failure rates remain relatively high and surgical reconstruction remains the definitive management. Robotic ureteral reconstruction has been demonstrated to provide patient benefit in nontransplant populations, but the literature on transplant reconstruction is very limited. This study reports an additional series of patients with a focus on surgical technique, as well as reviews the available evidence for robotic reconstruction for post-transplant ureteral complications. Methods: All institutional patients undergoing robotic-assisted reconstruction for post-transplant ureteral complications for the years 2019-2022 were included. Intra- and postoperative variables, patient demographics, and follow-up data were obtained retrospectively from parsing of patient records. Statistics were tabulated descriptively. Results: Eleven patients underwent ureteral reconstruction. Of the 11, 9 (81%) were male with a mean age of 51.9 years (16-70) and BMI of 33.8 (24.3-49.1). The most common (10/11) indication for reconstruction was stricture; the most common (10/11) technique used was Lich-Gregoir reimplantation. Mean operative time was 288 minutes (143-500). There were no intra- or immediate postoperative complications. Median length of stay was 2 days (1-22). There were two incidences of mortality at 2 and 5 months postoperatively unrelated to surgery. There were four readmissions within 30 days, three for urinary tract infection (UTI) and one for a pelvic abscess which required washout. The remainder of the cohort has been followed for a mean of 14.6 months (6-41) without any incidences of graft loss or recurrence of ureteral pathology. Conclusions: Robotic-assisted ureteral reconstruction is a technically challenging but highly feasible technique that may provide the benefits of minimally invasive surgery while still allowing definitive reconstruction. Centers with extensive robotic capabilities should consider the technique.


Assuntos
Transplante de Rim , Procedimentos Cirúrgicos Robóticos , Doenças Ureterais , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Robóticos/normas , Ureter/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Doenças Ureterais/etiologia , Doenças Ureterais/cirurgia
19.
Laryngoscope ; 134(9): 4045-4051, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38676455

RESUMO

INTRODUCTION: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes. METHODS: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique. RESULTS: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study. CONCLUSION: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken. LEVEL OF EVIDENCE: IV Laryngoscope, 134:4045-4051, 2024.


Assuntos
Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Esvaziamento Cervical/métodos , Feminino , Estudos Prospectivos , Masculino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/cirurgia , Idoso , Adulto , Duração da Cirurgia , Resultado do Tratamento , Satisfação do Paciente
20.
Biochim Biophys Acta Proteins Proteom ; 1872(4): 141015, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615986

RESUMO

The bifunctional enzyme, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) is involved in catalyzing penultimate and final steps of purine de novo biosynthetic pathway crucial for the survival of organisms. The present study reports the characterization of ATIC from Candidatus Liberibacer asiaticus (CLasATIC) along with the identification of potential inhibitor molecules and evaluation of cell proliferative activity. CLasATIC showed both the AICAR Transformylase (AICAR TFase) activity for substrates, 10-f-THF (Km, 146.6 µM and Vmax, 0.95 µmol/min/mg) and AICAR (Km, 34.81 µM and Vmax, 0.56 µmol/min/mg) and IMP cyclohydrolase (IMPCHase) activitiy (Km, 1.81 µM and Vmax, 2.87 µmol/min/mg). The optimum pH and temperature were also identified for the enzyme activity. In-silico study has been conducted to identify potential inhibitor molecules through virtual screening and MD simulations. Out of many compounds, HNBSA, diosbulbin A and lepidine D emerged as lead compounds, exhibiting higher binding energy and stability for CLasATIC than AICAR. ITC study reports higher binding affinities for HNBSA and diosbulbin A (Kd, 12.3 µM and 34.2 µM, respectively) compared to AICAR (Kd, 83.4 µM). Likewise, DSC studies showed enhanced thermal stability for CLasATIC in the presence of inhibitors. CD and Fluorescence studies revealed significant conformational changes in CLasATIC upon binding of the inhibitors. CLasATIC demonstrated potent cell proliferative, wound healing and ROS scavenging properties evaluated by cell-based bioassays using CHO cells. This study highlights CLasATIC as a promising drug target with potential inhibitors for managing CLas and its unique cell protective, wound-healing properties for future biotechnological applications.


Assuntos
Aminoimidazol Carboxamida , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/química , Aminoimidazol Carboxamida/metabolismo , Aminoimidazol Carboxamida/farmacologia , Fosforribosilaminoimidazolcarboxamida Formiltransferase/metabolismo , Fosforribosilaminoimidazolcarboxamida Formiltransferase/química , Simulação de Acoplamento Molecular , Ribonucleotídeos/metabolismo , Ribonucleotídeos/química , Cinética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/antagonistas & inibidores , Nucleotídeo Desaminases/metabolismo , Nucleotídeo Desaminases/química , Nucleotídeo Desaminases/genética , Especificidade por Substrato , Proliferação de Células/efeitos dos fármacos , Hidroximetil e Formil Transferases/metabolismo , Hidroximetil e Formil Transferases/química , Hidroximetil e Formil Transferases/genética , Hidroximetil e Formil Transferases/antagonistas & inibidores , Complexos Multienzimáticos
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