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1.
J Assoc Physicians India ; 72(4): 44-48, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38881083

RESUMEN

BACKGROUND: Psoriasis is an inflammatory skin disease associated with significant comorbidity. However, the characteristics of patients with psoriasis are not well documented in India, and a more detailed understanding is needed to delineate the epidemiologic profile at the regional level for better management of psoriasis. Herein, we reported the clinical profile and demographic pattern of psoriasis to further understand its burden in the Indian setting. METHODS: We conducted a retrospective observational study of patients diagnosed with psoriasis who fulfilled the classification criteria for psoriatic arthritis (CASPAR) criteria. Patients were included from the rheumatology outpatient department of Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute in Mumbai, India. The outcomes included demographic and clinical profiles, patterns of joint involvement, and comorbidities associated with psoriasis. A p-value of <0.05 was considered significant. RESULTS: We enrolled 60 patients, with a mean age of 50.87 years and a higher proportion of females (62%). The majority of patients with less than five joints had associated comorbidities (40 out of 60). Psoriatic arthritis (PsA) occurred in 41 patients [mean ± standard deviation (SD) age of onset-38.88 ± 13.24 years], with the highest occurrence in the 30-50 years (53.3%). The majority of patients with PsA developed it within 2 to ≥5 years of psoriasis occurrence. We did not find any significant correlation between the occurrence of PsA and comorbidities, as well as the duration of PsA and the number of joints (p = 0.152). Pitting and enthesitis were the most common morphological changes noted in almost half of the patients. CONCLUSION: Our study provides an overview of the epidemiologic and clinical characteristics of psoriasis patients in India. These findings could be useful for early diagnosis of PsA and help clinicians in assessing the progression of psoriasis into PsA.


Asunto(s)
Artritis Psoriásica , Humanos , Artritis Psoriásica/epidemiología , Artritis Psoriásica/diagnóstico , India/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Comorbilidad
2.
Oncogene ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858590

RESUMEN

Advanced hepatocellular carcinoma (HCC) is a lethal disease, with limited therapeutic options. Mixed Lineage Kinase 3 (MLK3) is a key regulator of liver diseases, although its role in HCC remains unclear. Analysis of TCGA databases suggested elevated MAP3K11 (MLK3 gene) expression, and TMA studies showed higher MLK3 activation in human HCCs. To understand MLK3's role in HCC, we utlized carcinogen-induced HCC model and compared between wild-type and MLK3 knockout (MLK3-/-) mice. Our studies showed that MLK3 kinase activity is upregulated in HCC, and MLK3 deficiency alleviates HCC progression. MLK3 deficiency reduced proliferation in vivo and MLK3 inhibition reduced proliferation and colony formation in vitro. To obtain further insight into the mechanism and identify newer targets mediating MLK3-induced HCCs, RNA-sequencing analysis was performed. These showed that MLK3 deficiency modulates various gene signatures, including EMT, and reduces TGFB1&2 expressions. HCC cells overexpressing MLK3 promoted EMT via autocrine TGFß signaling. Moreover, MLK3 deficiency attenuated activated hepatic stellate cell (HSC) signature, which is increased in wild-type. Interestingly, MLK3 promotes HSC activation via paracrine TGFß signaling. These findings reveal TGFß playing a key role at different steps of HCC, downstream of MLK3, implying MLK3-TGFß axis to be an ideal drug target for advanced HCC management.

3.
Adv Protein Chem Struct Biol ; 140: 347-379, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38762274

RESUMEN

Platelets, derived from bone marrow megakaryocytes, are essential for vascular integrity and play multifaceted roles in both physiological and pathological processes within the vasculature. Despite their small size and absence of a nucleus, platelets are increasingly recognized for their diverse immune functions. Recent research highlights their pivotal role in interactions with various immune cells, including professional cells like macrophages, dendritic cells, natural killer cells, T cells, and B cells, influencing host immune responses. Platelets also engage with non-professional immune cells, contributing to immune responses and structural maintenance, particularly in conditions like inflammation and atherosclerosis. This review underscores the emerging significance of platelets as potent immune cells, elucidating their interactions with the immune system. We explore the mechanisms of platelet activation, leading to diverse functions, such as aggregation, immunity, activation of other immune cells, and pathogen clearance. Platelets have become the predominant immune cells in circulation, involved in chronic inflammation, responses to infections, and autoimmune disorders. Their immunological attributes, including bioactive granule molecules and immune receptors, contribute to their role in immune responses. Unlike professional antigen-presenting cells, platelets process and present antigens through an MHC-I-dependent pathway, initiating T-cell immune responses. This review illuminates the unique features of platelets and their central role in modulating host immune responses in health and disease.


Asunto(s)
Plaquetas , Comunicación Celular , Humanos , Plaquetas/inmunología , Comunicación Celular/inmunología , Animales , Linfocitos T/inmunología , Células Dendríticas/inmunología
4.
Cureus ; 16(4): e58097, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38738112

RESUMEN

The widespread utilization of personal protective equipment (PPE) during the COVID-19 pandemic has been crucial for reducing transmission risk among healthcare workers (HCWs) and the public. However, the extensive use of PPE has brought about potential adverse reactions, particularly among HCWs. This study aims to investigate the prevalence and characteristics of adverse skin reactions associated with PPE use among different categories of HCWs, including faculty, residents, and nursing officers (NOs), in a dedicated tertiary care COVID-19 hospital. The study design was a hospital-based cross-sectional analytical study conducted over one month, involving a total of 240 participants. The participants were required to complete a pre-tested semi-structured questionnaire that covered demographic information, PPE-related data, preventive measures, observed reactions, and self-management strategies. Results indicated that adverse skin reactions were common among HCWs, with reactions reported by all participants. The most commonly used PPE included N95 masks, goggles, gloves, face shields, isolation gowns, and medical protective clothing. Excessive sweating (60% residents, 21.1% NOs, and 16.25% faculties), facial rash, dry palms (>70% of HCWs), and itching were among the most prevalent adverse reactions. Urticarial lesions (28.5% among NOs), pressure marks and pain (100% on the cheek among all HCWs), fungal infections (18.5% among residents at the web space of fingers), and skin breakdown were also reported. Factors such as age, gender, pre-existing skin problems, and oily/acne-prone skin history were found to be significantly associated with adverse skin reactions. In conclusion, the findings highlight the common adverse reactions reported by HCWs during the use of different PPEs. Certain steps taken by HCWs for the prevention of adverse reactions due to PPE emphasize the importance of tailored preventive measures and strategies to mitigate these adverse reactions, such as proper PPE selection, well-fitting equipment, regular breaks, and appropriate skincare practices. These insights contribute to the development of guidelines for optimal PPE usage and support the well-being of HCWs in their essential roles.

5.
Chem Biol Drug Des ; 103(5): e14531, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38726798

RESUMEN

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Humanos , Femenino , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/prevención & control , Prolina Dioxigenasas del Factor Inducible por Hipoxia/metabolismo , Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Ratones , Hipoxia de la Célula/efectos de los fármacos , Simulación del Acoplamiento Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Células MCF-7 , Línea Celular Tumoral , FN-kappa B/metabolismo , Tirapazamina/farmacología , Tirapazamina/química , Tirapazamina/metabolismo
6.
J Biochem Mol Toxicol ; 38(6): e23747, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38800879

RESUMEN

Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin-induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca2+ mobilization from inositol 1,4,5-trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase-mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT-induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients.


Asunto(s)
Plaquetas , Enfermedad de Parkinson , Especies Reactivas de Oxígeno , Rotenona , Humanos , Rotenona/farmacología , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/sangre , Especies Reactivas de Oxígeno/metabolismo
7.
J Biochem Mol Toxicol ; 38(4): e23679, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38486411

RESUMEN

Normoxic inactivation of prolyl hydroxylase-2 (PHD-2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF-1α and NF-κB. Henceforth, the present study is aimed to identify small molecule activators of PHD-2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD-2 activation potential of screened compound was determined using in vitro 2-oxoglutarate assay. The cytotoxic activity and apoptotic potential of screened compound was determined using various staining techniques, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 4',6-diamidino-2-phenylindole (DAPI), 1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), and acridine orange/ethidium bromide (AO/EB), against MCF-7 cells. 7,12-Dimethylbenz[a]anthracene (DMBA) model of mammary gland cancer was used to study the in vivo antineoplastic efficacy of screened compound. [(E)-1-(4-fluorophenyl)-3-(furan-2-yl) prop-2-en-1-one] (BBAP-7) was screened and validated as a PHD-2 activator by an in vitro 2-oxo-glutarate assay. The IC50 of BBAP-7 on MCF-7 cells is 18.84 µM. AO/EB and DAPI staining showed nuclear fragmentation, blebbing and condensation in MCF-7 cells following BBAP-7 treatment. The red-to-green intensity ratio of JC-1 stained MCF-7 cells decreased after BBAP-7 treatment, indicating mitochondrial-mediated apoptosis. DMBA caused mammary gland dysplasia, duct hyperplasia and ductal carcinoma in situ. Carmine staining, histopathology, and scanning electron microscopy demonstrated that BBAP-7, alone or with tirapazamine, restored mammary gland surface morphology and structural integrity. Additionally, BBAP-7 therapy significantly reduced oxidative stress and glycolysis. The findings reveal that BBAP-7 activates PHD-2, making it a promising anticancer drug.


Asunto(s)
Antineoplásicos , Bencimidazoles , Carbocianinas , Carcinoma , Chalcona , Chalconas , Humanos , Prolil Hidroxilasas , Chalconas/farmacología , Antineoplásicos/farmacología , Naranja de Acridina , Apoptosis , Microambiente Tumoral
8.
Adv Protein Chem Struct Biol ; 139: 263-288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38448137

RESUMEN

In the past three decades, interest in using carbon-based nanomaterials (CBNs) in biomedical application has witnessed remarkable growth. Despite the rapid advancement, the translation of laboratory experimentation to clinical applications of nanomaterials is one of the major challenges. This might be attributed to poor understanding of bio-nano interface. Arguably, the most significant barrier is the complexity that arises by interplay of several factors like properties of nanomaterial (shape, size, surface chemistry), its interaction with suspending media (surface hydration and dehydration, surface reconstruction and release of free surface energy) and the interaction with biomolecules (conformational change in biomolecules, interaction with membrane and receptor). Tailoring a nanomaterial that minimally interacts with protein and lipids in the medium while effectively acts on target site in biological milieu has been very difficult. Computational methods and artificial intelligence techniques have displayed potential in effectively addressing this problem. Through predictive modelling and deep learning, computer-based methods have demonstrated the capability to create accurate models of interactions between nanoparticles and cell membranes, as well as the uptake of nanomaterials by cells. Computer-based simulations techniques enable these computational models to forecast how making particular alterations to a material's physical and chemical properties could enhance functional aspects, such as the retention of drugs, the process of cellular uptake and biocompatibility. We review the most recent progress regarding the bio-nano interface studies between the plasma proteins and CBNs with a special focus on computational simulations based on molecular dynamics and density functional theory.


Asunto(s)
Inteligencia Artificial , Proteínas Sanguíneas , Transporte Biológico , Carbono , Membrana Celular
9.
Cancers (Basel) ; 16(4)2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38398170

RESUMEN

The gut microbiota composition can affect the tumor microenvironment and its interaction with the immune system, thereby having implications for treatment predictions. This article reviews the studies available to better understand how the gut microbiome helps the immune system fight cancer. To describe this fact, different mechanisms and approaches utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only calorie intake but also the variety and quality of diet can influence cancer patients' immunotherapy treatment because dietary patterns can impair immunological activities either by stimulating or suppressing innate and adaptive immunity. Therefore, it is interesting and critical to understand gut microbiome composition as a biomarker to predict cancer immunotherapy outcomes and responses. Here, more emphasis will be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies, which is beneficial for cancer patients.

10.
Ageing Res Rev ; 94: 102205, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38272267

RESUMEN

Neurodegenerative diseases (NDDs) are specific brain disorders characterized by the progressive deterioration of different motor activities as well as several cognitive functions. Current conventional therapeutic options for NDDs are limited in addressing underlying causes, delivering drugs to specific neuronal targets, and promoting tissue repair following brain injury. Due to the paucity of plausible theranostic options for NDDs, nanobiotechnology has emerged as a promising field, offering an interdisciplinary approach to create nanomaterials with high diagnostic and therapeutic efficacy for these diseases. Recently, two-dimensional nanomaterials (2D-NMs) have gained significant attention in biomedical and pharmaceutical applications due to their precise drug-loading capabilities, controlled release mechanisms, enhanced stability, improved biodegradability, and reduced cell toxicity. Although various studies have explored the diagnostic and therapeutic potential of different nanomaterials in NDDs, there is a lack of comprehensive review addressing the theranostic applications of 2D-NMs in these neuronal disorders. Therefore, this concise review aims to provide a state-of-the-art understanding of the need for these ultrathin 2D-NMs and their potential applications in biosensing and bioimaging, targeted drug delivery, tissue engineering, and regenerative medicine for NDDs.


Asunto(s)
Nanoestructuras , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/terapia , Nanoestructuras/uso terapéutico , Sistemas de Liberación de Medicamentos , Ingeniería de Tejidos , Medicina Regenerativa
11.
Curr Microbiol ; 81(3): 84, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294725

RESUMEN

Drought is a global phenomenon affecting plant growth and productivity, the severity of which has impacts around the whole world. A number of approaches, such as agronomic, conventional breeding, and genetic engineering, are followed to increase drought resilience; however, they are often time consuming and non-sustainable. Plant growth-promoting microorganisms are used worldwide to mitigate drought stress in crop plants. These microorganisms exhibit multifarious traits, which not only help in improving plant and soil health, but also demonstrate capabilities in ameliorating drought stress. The present review highlights various adaptive strategies shown by these microbes in improving drought resilience, such as modulation of various growth hormones and osmoprotectant levels, modification of root morphology, exopolysaccharide production, and prevention of oxidative damage. Gene expression patterns providing an adaptive edge for further amelioration of drought stress have also been studied in detail. Furthermore, the practical applications of these microorganisms in soil are highlighted, emphasizing their potential to increase crop productivity without compromising long-term soil health. This review provides a comprehensive coverage of plant growth-promoting microorganisms-mediated drought mitigation strategies, insights into gene expression patterns, and practical applications, while also guiding future research directions.


Asunto(s)
Agricultura , Sequías , Ingeniería Genética , Estrés Oxidativo , Suelo
12.
HIV Med ; 25(3): 322-331, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37821095

RESUMEN

BACKGROUND: At present, combination antiretroviral therapy (cART) is the mainstay for the treatment of people living with HIV/AIDS. cART can suppress the viral load to a minimal level; however, the possibility of the emergence of full-blown AIDS is always there. In the latter part of the first decade of the 21st century, an HIV-positive person received stem cell transplantation (SCT) for treatment of his haematological malignancy. The patient was able to achieve remission of the haematological condition as well as of HIV following SCT. Thorough investigations of various samples including blood and biopsy could not detect the virus in the person's body. The person was declared to be the first cured case of HIV. LITERATURE SEARCH: Over the next decade, a few more similar cases were observed and have recently been declared cured of the infection. A comprehensive search was performed in PubMed, Cochrane library and Google Scholar. Four such additional cases were found in literature. DESCRIPTION & DISCUSSION: These cases all share a common proposed mechanism for the HIV cure, that is, transplantation of stem cells from donors carrying a homozygous mutation in a gene encoding for CCR5 (receptor utilized by HIV for entry into the host cell), denoted as CCR5△32. This mutation makes the host immune cells devoid of CCR5, causing the host to acquire resistance against HIV. To the best of our knowledge, this is the first review to look at relevant and updated information of all cured cases of HIV as well as the related landmarks in history and discusses the underlying mechanism(s).


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Trasplante de Células Madre Hematopoyéticas , Humanos , Mutación , Receptores CCR5/genética
13.
Recent Adv Food Nutr Agric ; 14(3): 190-196, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37559534

RESUMEN

OBJECTIVE: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) has caused an immense public health crisis worldwide. Emerging evidence has suggested that inflammatory response plays a critical role in the pathogenesis and prognosis of the disease. As vitamin D can modulate the immune system, this study has been designed to correlate vitamin D with inflammatory and prognostic markers in COVID-19 patients. METHODS: The present study is a retrospective study examining the relationship between vitamin D levels and inflammatory markers in the COVID-19 disease. COVID-19 patients who were investigated for vitamin D, ferritin, D-dimer, C-reactive protein (CRP), and procalcitonin (PCT) level were only included. The patients were divided into hypovitaminosis D, and normal vitamin D. Correlation and logistic regression analyses were carried out to identify the strength and association of hypovitaminosis D with inflammatory markers in COVID-19 disease. RESULTS: The hypovitaminosis D group had significantly higher inflammatory markers compared to the normal vitamin D group. The correlation between hypovitaminosis D and procalcitonin was negative (r = -0.433), with a strong and significant association (p = 0.002). The correlation between hypovitaminosis D, CRP, and ferritin was weak and insignificant. The logistic regression between hypovitaminosis D and procalcitonin established a significant regression equation, leading to a significant linear model. CONCLUSION: This study concludes that patients with hypovitaminosis D should be treated with vitamin D therapy to reduce the severity of COVID-19 disease.


Asunto(s)
COVID-19 , Raquitismo , Deficiencia de Vitamina D , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Pronóstico , SARS-CoV-2 , Polipéptido alfa Relacionado con Calcitonina , Proteína C-Reactiva/análisis , Vitamina D , Vitaminas , Deficiencia de Vitamina D/complicaciones , Ferritinas
15.
Cureus ; 15(5): e39752, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37398778

RESUMEN

Background Preeclampsia is a major factor in both maternal and fetal morbidity and mortality. The most widely investigated preeclampsia prevention medication is low dose Aspirin. However, guidelines differ considerably regarding the prophylactic dose of Aspirin for preeclampsia. Objective The objective is to compare the efficacy of 150mg versus 75mg Aspirin for the prevention of preeclampsia in pregnant women at high risk of preeclampsia. Methodology This was a parallel, open-label, randomized control trial carried over a period of one year and three months at a tertiary care center of Eastern India. Block randomization was done and block sizes of 2 and 4 were used to ensure balanced distributions within the study arms. Primary outcome was the development of preeclampsia and secondary outcomes were fetomaternal complications in both groups. Results The present clinical trial was conducted on 116 pregnant women with a risk factor of preeclampsia and they were randomly assigned to receive either 150mg or 75mg of Aspirin daily beginning from 12 to 16 weeks of gestation till 36 weeks' gestation. A significantly greater number of pregnant females who received Aspirin 75mg (33.92%) developed preeclampsia in contrast to those who received Aspirin 150mg (8.77%), p=0.001, OR = 5.341, 95%CI = 1.829-15.594. There was an insignificant difference in fetomaternal outcome among both the groups of women. Conclusion Among women who are at high risk of developing preeclampsia, Aspirin 150 mg once a day at bedtime is more effective than Aspirin 75 mg once a day at bedtime in preventing preeclampsia with similar fetomaternal outcomes (NICU admission, IUGR, neonatal death, still birth, eclampsia, HELLP syndrome, placental abruption and pulmonary edema).

16.
RSC Adv ; 13(30): 20975-20983, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37441037

RESUMEN

We report a comprehensive study of the structural, morphological, and optical properties, and UC-based ratiometric temperature sensing behavior of (α) cubic and (ß) hexagonal phases of NaYF4:Yb3+/Er3+ nanoparticles. The α-NaYF4:Yb3+/Er3+ and ß-NaYF4:Yb3+/Er3+ nanoparticles were synthesized using co-precipitation and hydrothermal methods, respectively. Powder X-ray diffraction studies confirmed the phase purity of the samples. The morphological studies show uniform particle sizes of both phases; the average particle size of α-NaYF4:Yb3+/Er3+ and ß-NaYF4:Yb3+/Er3+ was 9.2 nm and 29 nm, respectively. The Raman spectra reveal five sharp peaks at 253 cm-1, 307 cm-1, 359 cm-1, 485 cm-1, and 628 cm-1 for ß-NaYF4:Yb3+/Er3+, whereas α-NaYF4:Yb3+/Er3+ shows two broad peaks centred at 272 cm-1 and 721 cm-1. The optical property measurements show that α- and ß-NaYF4:Yb3+/Er3+ phases have distinct upconversion emission and temperature sensing behavior. The upconversion emission measurements show that ß-NaYF4:Yb3+/Er3+ has higher overall emission intensities and green/red emission intensity ratio. The temperature-dependent upconversion emission measurements show that α-NaYF4:Yb3+/Er3+ has higher energy separation between 2H11/2 and 4S3/2 energy states. The temperature sensing performed utilizing these thermally coupled energy levels shows a maximum sensitivity of 0.0069 K-1 at 543 K and 0.016 K-1 at 422 K for ß-NaYF4:Yb3+/Er3+ and α-NaYF4:Yb3+/Er3+, respectively.

17.
Adv Cancer Res ; 159: 113-143, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37268394

RESUMEN

Pancreatic Ductal Adenocarcinoma (PDAC), commonly called pancreatic cancer, is aggressive cancer usually detected at a late stage, limiting treatment options with modest clinical responses. It is projected that by 2030, PDAC will be the second most common cause of cancer-related mortality in the United States. Drug resistance in PDAC is common and significantly affects patients' overall survival (OS). Oncogenic KRAS mutations are nearly uniform in PDAC, affecting over 90% of patients. However, effective drugs directed to target prevalent KRAS mutants in pancreatic cancer are not in clinical practice. Accordingly, efforts are continued on identifying alternative druggable target(s) or approaches to improve patient outcomes with PDAC. In most PDAC cases, the KRAS mutations turn-on the RAF-MEK-MAPK pathways, leading to pancreatic tumorigenesis. The MAPK signaling cascade (MAP4K→MAP3K→MAP2K→MAPK) plays a central role in the pancreatic cancer tumor microenvironment (TME) and chemotherapy resistance. The immunosuppressive pancreatic cancer TME is another unfavorable factor affecting the therapeutic efficacy of chemotherapy and immunotherapy. The immune checkpoint proteins (ICPs), including CTLA-4, PD-1, PD-L1, and PD-L2, are critical players in T cell dysfunction and pancreatic tumor cell growth. Here, we review the activation of MAPKs, a molecular trait of KRAS mutations and their impact on pancreatic cancer TME, chemoresistance, and expression of ICPs that could influence the clinical outcomes in PDAC patients. Therefore, understanding the interplay between MAPK pathways and TME could help to design rational therapy combining immunotherapy and MAPK inhibitors for pancreatic cancer treatment.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Inmunoterapia , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Microambiente Tumoral , Neoplasias Pancreáticas
18.
Sci Total Environ ; 892: 164680, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37302599

RESUMEN

Aeolian transport of continental dust from the Middle East and South Asia to the Arabian Sea (AS) is an important route for delivering key trace metals and nutrients. Despite being surrounded by several deserts, it is not clear which dust source is most likely contributing to mineral aerosols over this marine basin in winter. Substantial information on dust source emissions and transport pathways over the AS is, thus, needed for better constraining the biogeochemical effects in the sunlit surface waters. Here, we investigated the Sr and Nd isotopic composition (87Sr/86Sr and εNd(0)), respectively) of dust samples collected over the AS during a GEOTRACES-India expedition (GI-10: 13 January-10 February 2020). Both tracers, 87Sr/86Sr (0.70957-0.72495) and εNd(0) (-24.0 to -9.3), showed pronounced spatial variability. These proxies were further tagged with their source profiles of surrounding land masses based on the origin of air mass back trajectories (AMBTs). We also encountered two dust storms (DS), one on 27 January 2020 (87Sr/86Sr: 0.70957; εNd(0): -9.3) and the second one on 10 February 2020 (87Sr/86Sr: 0.71474, εNd(0):-12.5), which showed distinct isotopic signatures. AMBTs and satellite imagery together revealed that DS1 is from the Arabian Peninsula and DS2 is from Iran and/or the Indo-Gangetic Plain. Notably, the Sr and Nd isotope composition of DS1 is further consistent with other dust samples collected over the pelagic waters, suggesting the impact of dust outbreaks from the Arabian Peninsula during winter season. Such documentation based on the 87Sr/86Sr and εNd(0) over the Arabian Sea, hitherto, is lacking in literature and, thus, highlights the need for more measurements.


Asunto(s)
Contaminantes Atmosféricos , Oligoelementos , Polvo/análisis , Contaminantes Atmosféricos/análisis , Estaciones del Año , Isótopos , Monitoreo del Ambiente , Aerosoles/análisis
19.
J Environ Manage ; 344: 118492, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37384989

RESUMEN

Persistent organic pollutants (POPs) are chemicals which have been persisting in the environment for many years due to their longer half-lives. POPs have gained attention over the last few decades due to the unsustainable management of chemicals which led to their widespread and massive contamination of biota from different strata and environments. Due to the widespread distribution, bio-accumulation and toxic behavior, POPs have become a risk for organisms and environment. Therefore, a focus is required to eliminate these chemicals from the environment or transform into non-toxic forms. Among the available techniques for the removal of POPs, most of them are inefficient or incur high operational costs. As an alternative to this, microbial bioremediation of POPs such as pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, pharmaceuticals and personal care products is much more efficient and cost-effective. Additionally, bacteria play a vital role in the biotransformation and solubilization of POPs, which reduces their toxicity. This review specifies the Stockholm Convention that evaluates the risk profile for the management of existing as well as emerging POPs. The sources, types and persistence of POPs along with the comparison of conventional elimination and bioremediation methods of POPs are discussed comprehensively. This study demonstrates the existing bioremediation techniques of POPs and summaries the potential of microbes which serve as enhanced, cost-effective, and eco-friendly approach for POPs elimination.


Asunto(s)
Contaminantes Ambientales , Plaguicidas , Bifenilos Policlorados , Contaminantes Orgánicos Persistentes , Bifenilos Policlorados/análisis , Contaminantes Ambientales/análisis , Biota , Monitoreo del Ambiente/métodos , Plaguicidas/análisis
20.
Cureus ; 15(3): e36827, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37123688

RESUMEN

Pancreatic cystic lesions (PCL) have a wide range of demographical, clinical, morphological and histological characteristics. The distinction between these lesions is of paramount importance due to the risk of malignancy in specific categories of PCL. Considering the malignant potential for pancreatic cystic neoplasm (PCN) lesions, guidelines have been made to balance unnecessary treatment and manage the progression to malignancy. Various surgical procedures can be done for PCN depending on the location and size of the cyst; pancreatoduodenectomy is done for PCN located in the head of the uncinate process, whereas distal pancreatectomy is done for PCN in the body or tail. In the neck and proximal body of the pancreas, less extensive resections such as central pancreatectomy can be performed. Active surveillance of PCN is typically offered to asymptomatic PCNs of subtype intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) without any concerning features. In recent years, numerous guidelines have been created to augment PCN diagnosis, classification and management. Despite this, the management of PCNs remains complex. Thus, discussions with multidisciplinary teams involving surgeons, gastroenterologists, pathologists, and radiologists are required to ensure optimum care for the patient.

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