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1.
J Maxillofac Oral Surg ; 23(4): 909-913, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39118927

RESUMO

Introduction: Early retromolar trigone (RMT) lesions are difficult to access and free tissue transfer is often an overkill for such small lesions. The aim was to devise a novel surgical approach that would aid the resection without raising a cheek flap and simultaneously provide a local reconstructive option for small lesions in the RMT. Methodology: This study was to demonstrate the outcomes of the "trans-facial" approach used to simultaneously access and reconstruct small RMT tumors through an islanded nasolabial flap. Patients with histologically proven squamous cell carcinoma of RMT requiring surgery were included from January 2021 to September 2022. Case selection was done based on the location of the disease and its size (cT1/T2). All needed bone and soft tissue resection via per oral trans-facial approach, along with an ipsilateral neck dissection. The technique is described along with their post-operative and pathologic outcomes. Results: Out of the eight patients included in this study, six underwent a bi-alveolar marginal resection and reconstructed using the trans-facial approach. No major complications were noted in the post-operative period. 50% were pT1 tumors and 75% were pN0 status. One patient had a close margin; while, the others had adequate resection margins. All patients were followed up for a median of 18 months with a locoregionally controlled status. Conclusion: The trans-facial approach can be a suitable option with a reasonable oncologic outcome to address small RMT lesions.

2.
Rambam Maimonides Med J ; 15(3)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39088704

RESUMO

BACKGROUND: Resection of oral cavity carcinoma often leads to complex defects causing functional and aesthetic morbidity. Providing optimum reconstruction with free flaps becomes challenging in a high-volume center setting with constrained resources. Hence, understanding the local flap technique for reconstructing oral cancer defects is prudent. MATERIALS AND METHODS: This study is a retrospective analysis of prospectively operated cases of oral cavity resections which were subsequently reconstructed using local flaps from 2019 to 2022. Patients who underwent reconstruction with either melolabial flap, islanded facial artery myomucosal (FAMM) flap, submental flap, supraclavicular artery island flap, infrahyoid flap, or platysma myocutaneous flap (PMF) were included in this analysis. Eligible patients were followed up to evaluate functional outcomes like oral feeding and to analyze the Performance Status Scale for Head and Neck Cancer. RESULTS: The study included 104 patients. The tongue was the most common subsite, resulting in most hemiglossectomy defects, which were reconstructed using the melolabial flap procedure. Buccal mucosa defects in our series were reconstructed using the supraclavicular flap, whereas the submental flap procedure was the choice for lower lip-commissure defects. Complications such as partial and total flap loss, deep neck infection, and donor site complications like infection and gaping, oral cutaneous fistula, parotid fistula, and seroma were analyzed; the supraclavicular flap presented with a majority of complications. CONCLUSION: Local flaps are an alternative to free flap reconstruction in select cases with optimum functional outcomes and minimal donor site morbidity. This article comprehensively reviews the surgical steps for various local flap procedures in oral cancer defects.

3.
Int Microbiol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138687

RESUMO

Rice cultivation generates huge amounts of on farm residues especially under mechanical harvesting. Paddy straw being recalcitrant hinders sowing of upcoming rabi crops like wheat and mustard. Non-environmental sustainable practice of on-farm burning of the paddy residues is being popularly followed for quick disposal of the agro-residues and land preparation. However, conservation agriculture involving in situ residue incorporation can be a sustainable option to utilize the residues for improvement of soil biological health. However, low temperature coupled with poor nitrogen status of soil reduces the decomposition rate of residues that may lead to nitrogen immobilization and hindrance in land preparation. In this direction, ecological impact of two approaches viz priming with urea and copiotrophic fungus-based bioformulation (CFB) consisting of Coprinopsis cinerea LA2 and Cyathus stercoreus ITCC3745 was studied for in situ degradation of residues. Succession of bacterial diversity was deciphered through high throughput whole metagenomic sequencing along with studies on dynamics of soil microbial enzymes. Treatments receiving CFB (T1) and urea (T2) when compared with bulk soil (absolute control) showed an increase in richness of the microbial diversity as compared to control straw retained treatment control (T3). The ß diversity indices also indicated sufficient group variations among the treatments receiving CFB and urea as compared to only straw retained treatment and bulk soil. Priming of paddy straw with CFB and urea also induced significant rewiring of the bacterial co-occurrence networks. Quantification of soil ligno-cellulolytic activity as well as abundance of carbohydrate active enzymes (CAZy) genes indicated high activities of hydrolytic enzymes in CFB primed straw retention treatment as compared to urea primed straw retention treatment. The genomic insights on effectiveness of copiotrophic fungus bioformulation for in situ degradation of paddy straw will further help in developing strategies for management of crop residues in eco-friendly manner.

4.
Cancer Epidemiol ; 92: 102644, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39153274

RESUMO

OBJECTIVE: This study aimed to investigate the association between lifetime occupational history and risk of buccal mucosa cancer (BMC). METHODS: We utilized a multi-centric, hospital-based case-control study across five centres of Tata Memorial Centre, Mumbai, India. Cases included men aged 20-75-years with histological confirmed primary cancer of the buccal mucosa. Visitor controls were frequency matched to cases for age (10 years interval) and current residential zone. Study participants were interviewed face-to-face. Logistic regression was performed to estimate odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: Among ever employed males, we identified 1969 BMC cases and 2145 controls. We observed an increased risk of BMC in 'Craft and Related Trades Workers' (OR 1.37; 95 % CI 1.13-1.65), 'Plant and Machine Operators and Assemblers' (OR: 1.26; 95 % CI 1.01-1.56), and 'Elementary Occupations' (OR:1.33; 95 % CI 1.12-1.58). More specifically, the increased risk was observed for 'Metal, Machinery and Related Trades Workers', 'Handicraft and Printing Workers', 'Drivers and Mobile Plant Operators', and 'Laborers in Mining, Construction, Manufacturing and Transport'. CONCLUSION: Our findings suggest that certain occupations may be at a higher risk of BMC. Some fraction of BMC can be prevented by reducing exposure to hazardous agents used in these occupations. Further research is needed to identify which exposures are responsible for the increased risk. Moreover, tobacco control and early detection activities can be focused towards these occupations as tobacco consumption is also high in them, which may also be the reason for increased risk observed in these groups.

5.
bioRxiv ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39071308

RESUMO

Biomolecular condensates arising from liquid-liquid phase separation contribute to diverse cellular processes, such as gene expression. Partitioning of client molecules into condensates is critical to regulating the composition and function of condensates. Previous studies suggest that client size limits partitioning, with dextrans >5 nm excluded from condensates. Here, we asked whether larger particles, such as macromolecular complexes, can partition into condensates based on particle-condensate interactions. We sought to discover the biophysical principles that govern particle inclusion in or exclusion from condensates using polymer nanoparticles with tailored surface chemistries as models of macromolecular complexes. Particles coated with polyethylene glycol (PEG) did not partition into condensates. We next leveraged the PEGylated particles as an inert platform to which we conjugated specific adhesive moieties. Particles functionalized with biotin partitioned into condensates containing streptavidin, driven by high-affinity biotin-streptavidin binding. Oligonucleotide-decorated particles exhibited varying degrees of partitioning into condensates, depending on condensate composition. Partitioning of oligonucleotide-coated particles was tuned by altering salt concentration, oligonucleotide length, and oligonucleotide surface density. Remarkably, beads with distinct surface chemistries partitioned orthogonally into immiscible condensates. Based on our experiments, we conclude that arbitrarily large particles can controllably partition into biomolecular condensates given sufficiently strong condensate-particle interactions, a conclusion also supported by our coarse-grained molecular dynamics simulations and theory. These findings may provide insights into how various cellular processes are achieved based on partitioning of large clients into biomolecular condensates, as well as offer design principles for the development of drug delivery systems that selectively target disease-related biomolecular condensates.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38834502

RESUMO

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare and malignant tumor of the salivary glands. Despite its slow-growing nature, this clinical entity is notorious for presenting with distant metastasis (DM) which significantly worsens patient outcomes. The role of surgery in patients with ACC and distant metastasis (DM) remains controversial. METHODS: We conducted a retrospective analysis of 47 patients with ACC who underwent surgery for the primary tumor and presented with DM at baseline or developed DM during follow-up. We compared survival outcomes between patients with DM at baseline (Group A) and those who developed DM during follow-up (Group B). RESULTS: The median overall survival (OS) for the entire cohort was 88%. Patients with DM at baseline (Group A) had significantly worse OS (51%) compared to those without DM at baseline (Group B) (91%; P = .04). Local recurrence (LR) was associated with poor survival in both groups. However, salvage surgery for LR+DM was associated with improved OS compared to palliative treatment (100% vs 77%; P = .79). CONCLUSION: Our findings suggest that surgery for the primary tumor of ACC may provide survival benefits in patients with DM. Salvage surgery should be considered particularly for patients who develop local recurrence and distant metastasis during follow-up.


Assuntos
Carcinoma Adenoide Cístico , Recidiva Local de Neoplasia , Humanos , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/secundário , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Metástase Neoplásica , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Terapia de Salvação , Resultado do Tratamento , Taxa de Sobrevida , Idoso de 80 Anos ou mais
7.
Cell Metab ; 36(7): 1521-1533.e5, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38718792

RESUMO

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1ß induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.


Assuntos
Ceramidas , Retinopatia Diabética , Imunoterapia , Ceramidas/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Retinopatia Diabética/imunologia , Animais , Humanos , Camundongos , Células Endoteliais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Masculino , Retina/metabolismo , Retina/patologia , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Ratos , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/metabolismo , Corpo Vítreo/metabolismo , Feminino , Camundongos Knockout
8.
Oral Dis ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566541

RESUMO

INTRODUCTION: The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health. GLOBAL PERSPECTIVE: Areca nut, often chewed in various forms such as betel quid, is deeply rooted in cultural practices across Asia and other parts of the world. Epidemiological studies consistently reveal a significant correlation between areca nut use and the incidence of oral cancer, emphasizing the need for targeted preventive measures. The complex interplay of areca nut's bioactive compounds, particularly arecoline, with cellular processes, contributes to the initiation and progression of oral carcinogenesis. Mechanistic insights into the genotoxic and cytotoxic effects of its components underscore the urgency for comprehensive public health interventions. PUBLIC HEALTH: Efforts to address this public health challenge involve multidisciplinary approaches, encompassing education, policy implementation, and behavioral interventions. Understanding the socio-cultural factors influencing areca nut consumption is pivotal for designing effective awareness campaigns and cessation programs. CONCLUSION: As oral cancer remains a significant global health burden, unraveling the nuanced relationship between areca nut and its role in oral carcinogenesis is crucial for advancing preventive strategies and mitigating the impact of this modifiable risk factor.

9.
Head Neck ; 46(6): 1263-1269, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38622958

RESUMO

INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.


Assuntos
Eficiência , Mortalidade Prematura , Neoplasias Bucais , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Neoplasias Bucais/mortalidade , Neoplasias Bucais/economia , Adulto , Efeitos Psicossociais da Doença , Idoso
10.
Sci Rep ; 14(1): 7263, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538715

RESUMO

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.


Assuntos
Cyperus , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Antioxidantes/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Folhas de Planta/química
11.
Health Mark Q ; 41(1): 95-111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38032235

RESUMO

This research unpacks the challenges and motivations of telehealth usage among older consumers-an understudied population in the extant telehealth literature. Through surveying a sample of older consumers who regularly migrate to winter in the southern areas of the United States, our qualitative analysis uncovers motivations (i.e., convenience, ease of use, efficiency, and a forced option) and challenges (i.e., telehealth limitations, privacy concerns, and lack of trust, access, and skills) of older consumers' telehealth usage. Furthermore, logistic regression identifies attitude toward telehealth, gender, and health status as significant predictors of telehealth usage behavior. Contributions to theory and practice are also discussed.


Assuntos
Telemedicina , Humanos , Estados Unidos , Atitude , Motivação , Pandemias
12.
3 Biotech ; 14(1): 19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38130685

RESUMO

The prized Red banana, selected for superior qualities, demands strong genetic uniformity for successful clonal propagation and preservation. Ensuring this uniformity early in the growth of in vitro Red banana plants is essential, as gene mutations and chromosome rearrangements during tissue culture can jeopardize both cloning and germplasm conservation. In this situation, molecular markers play a pivotal role in confirming genetic stability. Thus the study aims to discover a marker that identifies tissue-cultured Red bananas from their virescent variants during initial sub-culturing. A marker linked to anthocyanin has been identified which effectively differentiated Red bananas from virescent variants and it was further validated in various banana cultivars, ornamental Musa species and their interspecific hybrids. The PCR-based marker showed remarkable specificity, discerning Red bananas from virescent variants during tissue culture. It also distinguished green and red offspring, cutting time and resource costs, and shortening the banana breeding cycle. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03868-6.

13.
Front Chem ; 11: 1271157, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075496

RESUMO

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37921163

RESUMO

Cardiovascular diseases (CVDs) are one of the most prevalent medical conditions of modern era and are one of the primary causes of adult mortality in both developing and developed countries. Conventional medications such as use of aspirin, beta-blockers, statins and angiotensin- converting enzyme inhibitors involve use of drugs with many antagonistic effects. Hence, alternative therapies which are safe, effective, and relatively cheap are increasingly being investigated for the treatment and prevention of CVDs. The secondary metabolites of medicinal plants contain several bioactive compounds which have emerged as alternatives to toxic modern medicines. The detrimental effects of CVDs can be mitigated via the use of various bioactive phytochemicals such as catechin, isoflavones, quercetin etc. present in medicinal plants. Current review intends to accumulate previously published data over the years using online databases concerning herbal plant based secondary metabolites that can help in inhibition and treatment of CVDs. An in-depth review of various phytochemical constituents with therapeutic actions such as antioxidant, anti-inflammatory, vasorelaxant, anti-hypertensive and cardioprotective properties has been delineated. An attempt has been made to provide a probable mechanistic overview for the pertinent phytoconstituent which will help in achieving a better prognosis and effective treatment for CVDs.


Assuntos
Doenças Cardiovasculares , Plantas Medicinais , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Plantas Medicinais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico
15.
Curr Microbiol ; 81(1): 14, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38006515

RESUMO

Soil salinization is a global issue that negatively impacts crop yield and has become a prime concern for researchers worldwide. Many important crop plants are susceptible to salinity-induced stresses, including ionic and osmotic stress. Approximately, 20% of the world's cultivated and 33% of irrigated land is affected by salt. While various agricultural practices have been successful in alleviating salinity stress, they can be costly and not environment-friendly. Therefore, there is a need for cost-effective and eco-friendly practices to improve soil health. One promising approach involves utilizing microbes found in the vicinity of plant roots to mitigate the effects of salinity stress and enhance plant growth as well as crop yield. By exploiting the salinity tolerance of plants and their associated rhizospheric microorganisms, which have plant growth-promoting properties, it is possible to reduce the adverse effects of salt stress on crop plants. The soil salinization is a common problem in the world, due to which we are unable to use the saline land. To make proper use of this land for different crops, microorganisms can play an important role. Looking at the increasing population of the world, this will be an appreciated effort to make the best use of the wasted land for food security. The updated information on this issue is needed. In this context, this article provides a concise review of the latest research on the use of salt-tolerant rhizospheric microorganisms to mitigate salinity stress in crop plants.


Assuntos
Agricultura , Desenvolvimento Vegetal , Produção Agrícola , Solo , Raízes de Plantas , Salinidade
16.
Cell Death Differ ; 30(11): 2408-2431, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37838774

RESUMO

Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors.


Assuntos
Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Humanos , Feminino , Epitopos , Receptor fas/genética , Receptor fas/metabolismo , Proteína Ligante Fas , Linfócitos T , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Apoptose , Anticorpos/farmacologia
17.
Chem Biodivers ; 20(12): e202301234, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37867394

RESUMO

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.


Assuntos
Anti-Infecciosos , Antiulcerosos , Catequina , Salix , Catequina/farmacologia , Antioxidantes/análise , Antiácidos/análise , Antiácidos/metabolismo , Salix/química , Salix/metabolismo , Madeira , Casca de Planta/química , Escherichia coli , Staphylococcus aureus , Extratos Vegetais/química , Compostos Fitoquímicos/química , Antibacterianos/metabolismo , Folhas de Planta , Anti-Infecciosos/metabolismo
18.
Chem Biodivers ; 20(10): e202301049, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37728228

RESUMO

Mimosa pudica L. (MP) is well-known plant in traditional medicinal system, especially in India. Unfortunately, leaves of MP are less explored. To determine the food and nutritional value of the neglected part of Mimosa pudica L. (MP), that is MP leaves, phytochemicals and metal ions of MP were quantified by newly developed HPLC and ICPOES-based methods. The content of phytochemicals observed using HPLC analysis for chlorogenic acid, catechin, and epicatechin was 141.823 (±8.171), 666.621 (±11.432), and 293.175 (±12.743) µg/g, respectively. Using GC/MS/MS analysis, fatty acid like oleic acid were identified. In ICP-OES analysis, a significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The observed TPC and TFC for MP leaf extracts was 44.327 (±1.041) mg GAE/ g of wt. and 214.217 (±4.372) mg QCE/ g of wt., respectively. The DPPH assay depicted a strong antioxidant activity of MP leaf extracts with IC50 values of 0.796 (±0.081) mg/mL and a TEAC value of 0.0356 (±0.0003). A significant antacid activity (666 mg MP+400 mg CaCO3 >400 mg CaCO3 ≫666 mg Gelusil) of MP leaves was noticed. The methanolic extract of MP leaves demonstrated anti-microbial activity against Staphylococcus aureus (15±2mm), Pseudomonas aeruginosa (12±2mm) and Escherichia coli (10±2mm). In silico studies confirmed the in vitro results obtained for antioxidant, antiacid, and anti-microbial activities. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the MP leaves. In summary, this study demonstrated the medicinal significance of MP leaves and the conversion of agro-waste or the under-utilized part of MP into pharmaceutical potent materials. Consequently, the present study highlighted that MP leaves alone have medicinal importance with good nutritional utility and possess large promise in the pharma industry along with improving bio-valorization and the environment.

19.
Environ Pollut ; 336: 122464, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37634566

RESUMO

Wastewater treatment plants (WWTPs) efficiently eliminate over 98% of microplastics (MPs) from wastewater discharge, subsequently accumulating them in sludge. This sludge is frequently employed as fertilizer in agricultural practices or land rehabilitation. While there is significant research on biosolid application in agriculture, the discussion regarding its application in rehabilitating industrial zones and MPs contamination is limited. The current study investigates the abundance, distribution, and composition of MPs in rehabilitation land with long-term biosolid-application in Australia. Three minesite fields (designated 1-3), each with distinct biosolid application histories since 2011, 2012, and 2017, and a control field without any biosolid application history, were chosen for this study. The abundances of MPs in biosolid-applied fields 1-3 (6.04 ± 1.92 x 102 MP kg-1; 4.94 ± 0.73 x 102 MP kg-1; 2.48 ± 0.70 x 102 MP kg-1) were considerably higher compared to non-biosolid-applied field (0.70 ± 0.63 x 102 MP kg -1). This indicates that the application of biosolids significantly contributes to the presence of MPs in the soil. Moreover, the results suggest that with each successive application, the abundance of MPs increases. The abundance and size of MPs in both biosolid and non-biosolid soils decreased as the soil depth increased. Microbeads were dominant in soils where biosolids were applied (up to 61.9%), while fibres were dominant in non-biosolid soils (accounting for 85.7%). The distribution of plastic polymer types varied among fields and soil depths. Most MPs were microbeads of polyamide (PA), fragments of polyethylene (PE), foam of polystyrene (PS), and fibres of rayon. This research presents evidence that the extended utilization of biosolids results in elevated MP pollution in minesite rehabilitation land, highlighting a frequently overlooked origin of MP contamination in terrestrial settings. Additional evaluations needed to understand ecological risks of MPs in soil ecosystems affected by biosolid application.


Assuntos
Microplásticos , Poluentes do Solo , Plásticos , Esgotos , Biossólidos , Ecossistema , Poluentes do Solo/análise , Solo , Austrália
20.
Acta Biomater ; 170: 53-67, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634836

RESUMO

While bone morphogenic protein-2 (BMP-2) is one of the most widely studied BMPs in bone tissue engineering, BMP-9 has been purported to be a highly osteogenic BMP. This work investigates the individual osteogenic effects of recombinant human (rh) BMP-2 and rhBMP-9, when tethered into a hydrogel, on encapsulated human mesenchymal stem cells (MSCs). A matrix-metalloproteinase (MMP)-sensitive hydrogel nanocomposite, comprised of poly(ethylene glycol) crosslinked with MMP-sensitive peptides, tethered RGD, and entrapped hydroxyapatite nanoparticles was used. The rhBMPs were functionalized with free thiols and then covalently tethered into the hydrogel by a thiol-norbornene photoclick reaction. rhBMP-2 retained its full bioactivity post-thiolation, while the bioactivity of rhBMP-9 was partially reduced. Nonetheless, both rhBMPs were highly effective at enhancing osteogenesis over 12-weeks in a chemically-defined medium. Expression of ID1 and osterix, early markers of osteogenesis; collagen type I, a main component of the bone extracellular matrix (ECM); and osteopontin, bone sialoprotein II and dentin matrix protein I, mature osteoblast markers, increased with increasing concentrations of tethered rhBMP-2 or rhBMP-9. When comparing the two BMPs, rhBMP-9 led to more rapid collagen deposition and greater mineralization long-term. In summary, rhBMP-2 retained its bioactivity post-thiolation while rhBMP-9 is more susceptible to thiolation. Despite this shortcoming with rhBMP-9, both rhBMPs when tethered into this hydrogel, enhanced osteogenesis of MSCs, leading to a mature osteoblast phenotype surrounded by a mineralized ECM. STATEMENT OF SIGNIFICANCE: Osteoinductive hydrogels are a promising vehicle to deliver mesenchymal stem cells (MSCs) for bone regeneration. This study examines the in vitro osteoinductive capabilities when tethered bone morphogenic proteins (BMPs) are incorporated into a degradable biomimetic hydrogel with cell adhesive ligands, matrix metalloproteinase sensitive crosslinks for cell-mediated degradation, and hydroxyapatite nanoparticles. This study demonstrates that BMP-2 is readily thiolated and tethered without loss of bioactivity while bioactivity of BMP-9 is more susceptible to immobilization. Nonetheless, when either BMP2 or BMP9 are tethered into this hydrogel, osteogenesis of human MSCs is enhanced, bone extracellular matrix is deposited, and a mature osteoblast phenotype is achieved. This bone-biomimetic hydrogel is a promising design for stem cell-mediated bone regeneration.


Assuntos
Fator 2 de Diferenciação de Crescimento , Osteogênese , Humanos , Fator 2 de Diferenciação de Crescimento/farmacologia , Materiais Biocompatíveis/farmacologia , Proteína Morfogenética Óssea 2/farmacologia , Proteínas Morfogenéticas Ósseas , Durapatita/farmacologia , Hidrogéis/farmacologia , Diferenciação Celular
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