Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
Mol Cancer Ther ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39212669

RESUMEN

As tumor-associated macrophages (TAMs) exercise a plethora of pro-tumor and immune evasive functions, novel strategies targeting TAMs to inhibit tumor progression have emerged within the current arena of cancer immunotherapy. Activation of the mannose receptor 1 (Mrc1; CD206) is a recent approach that recognizes immune suppressive CD206high M2-like TAMs as a drug target. Ligation of CD206 both induces reprogramming of CD206high TAMs towards a pro-inflammatory phenotype and selectively triggers apoptosis in these cells. CD206-activating therapeutics are currently limited to the linear, 10mer peptide RP-182, 1, which is not a drug candidate. Here we sought to identify a better suitable candidate for future clinical development by synthesizing and evaluating a series of RP-182 analogues. Surprisingly, fatty acid derivative 1a (RP-182-PEG3-K(palmitic acid)) not only showed improved stability but also increased affinity to the CD206 receptor through enhanced interaction with a hydrophobic binding motif of CD206. Peptide 1a showed superior in vitro activity in cell-based assays of macrophage activation which was restricted to CD206high M2-polarized macrophages. Improvement of responses was disproportionally skewed towards improved induction of phagocytosis including cancer cell phagocytosis. 1a reprogrammed the immune landscape in genetically engineered murine KPC pancreatic tumors towards increased innate immune surveillance and improved tumor control, and effectively suppressed tumor growth of murine B16 melanoma allografts.

2.
Mol Biol Rep ; 51(1): 657, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740636

RESUMEN

BACKGROUND: Mycobacterium tuberculosis (MTB) is the causative organism of tuberculosis. Cholesterol is a crucial carbon source required for the survival of MTB in host cells. Transcription factor NR1H3 along with its important target genes ABCA1 and ApoE play important role in removal of extra cholesterol from cells. Changes in the gene expression of NR1H3, ABCA1 and ApoE can affect cholesterol homeostasis and thus the survival of MTB in host cells.Therefore, the present study was designed to analyze the mRNA expression of NR1H3, ABCA1 and ApoE in pulmonary TB (PTB) patients from the population of Punjab, India. METHODS AND RESULTS: In this study, mRNA expression of the transcription factor NR1H3 and its target genes ABCA1 and ApoE was analyzed in 89 subjects, including 41 PTB patients and 48 healthy controls (HCs) by real-time quantitative PCR. It was found that the mRNA expression of both NR1H3 and ABCA1 genes was significantly lower in TB patients than in HCs (p < 0.001). Even after sex-wise stratification of the subjects, mRNA expression of NR1H3 and ABCA1 was found to be down-regulated in both male and female TB patients. No significant difference was observed in expression of ApoE (p = 0.98). CONCLUSIONS: The present study found that the mRNA expression of NR1H3 and ABCA1 is down-regulated in TB patients from Punjab state of India.


Asunto(s)
Transportador 1 de Casete de Unión a ATP , Receptores X del Hígado , ARN Mensajero , Tuberculosis Pulmonar , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Estudios de Casos y Controles , India , Mycobacterium tuberculosis/genética , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/metabolismo , Receptores X del Hígado/genética , Receptores X del Hígado/metabolismo
3.
J Assoc Physicians India ; 71(8): 11-12, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37651238

RESUMEN

IMPORTANCE: Multisystem inflammatory syndrome-adults (MIS-A) occur in the postacute coronavirus disease 2019 (COVID-19) period with a diverse clinical presentation. A high index of suspicion, early recognition, diagnosis, and treatment of MIS-A might alleviate COVID-19-related morbidity and mortality. OBJECTIVE: To report seven cases of MIS-A with evidence of recent COVID-19 infection. This is a case series-based study and presents bona fide experiences in terms of main findings and treatment options. MATERIALS AND METHODS: It is a retrospective observational study. We retrospectively collected data on all patients who were diagnosed and treated for MIS-A during the period after the second wave of COVID-19 in India, that is, from June 2021 to November 2021and who were hospitalized in the author's unit. All patients fulfilled the morbidity and mortality weekly report (MMWR) criteria for multisystem inflammatory syndrome in adults. The presenting symptoms, clinical and laboratory parameters, management, and outcome of these seen cases are discussed in this case series-based review.. RESULTS: Data from seven patients were analyzed. Six of them were male, and one patient was female. The median age was 65 years. Four patients had a history of vaccination for COVID-19, three had a history of COVID-19 symptomatic infection in the past, and one patient had contact with COVID-19 in the previous 12 weeks. None of them tested positive for COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) test, and all had positive COVID-19 serology. The commonest extrapulmonary organ involved were the cardiovascular and renal systems, followed by the gastrointestinal and central nervous systems (CNS). All had evidence of hyperinflammation. Intravenous immunoglobulin (IVIg) was used in four patients, and steroids were used in all seven patients. The median length of stay (LOS) was 11 days. One patient succumbed to multiorgan failure. CONCLUSIONS: Multisystem inflammatory syndrome (MIS) can affect children (MIS-C) as well as adults (MIS-A). MIS-A is a serious, life-threatening, hyperinflammatory febrile syndrome associated with recent COVID-19 infection and involves multiple organs like the heart, lungs, kidneys, brain, gastrointestinal organs, skin, eyes etc. Clinical suspicion and testing for evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are needed to identify and treat adults suspected to have MIS-A. This case series demonstrates that even the elderly population can be affected and that administration of IVIg and steroids are effective options in management in addition to the usual "standard of care" treatment. Early recognition and prompt treatment of MIS-A could improve clinical outcomes and reduce the mortality rate.


Asunto(s)
COVID-19 , Enfermedades del Tejido Conjuntivo , Niño , Humanos , Adulto , Anciano , Femenino , Masculino , SARS-CoV-2 , Inmunoglobulinas Intravenosas , Estudios Retrospectivos
4.
Turk J Anaesthesiol Reanim ; 51(2): 128-134, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37140578

RESUMEN

OBJECTIVE: Propofol is required in higher doses for smooth insertion of the ProSeal laryngeal mask airway. The ideal adjuvant drug so as to minimise induction doses of propofol is still not known. Dexmedetomidine and midazolam are equally effective for premedication in children. We have designed this study to compare dexmedetomidine and midazolam as adjuvants with propofol for insertion characteristics of ProSeal laryngeal mask airway. METHODS: A total of 130 paediatric patients undergoing elective surgery were randomly allocated into 2 groups of 65 each. One group was induced using propofol, fentanyl and midazolam, whereas the other group received propofol, fentanyl and dexmedetomidine. Subsequently, insertion characteristics of ProSeal laryngeal mask airway were documented in terms of number of attempts and by using modified Muzi score. Post-operative sedation was recorded by Ramsay Sedation Scale and pain was assessed by using Wong-Baker Faces pain scale. RESULTS: Out of 130 patients, ProSeal laryngeal mask airway was inserted in a second attempt in only 5 patients of midazolam group. Time taken for insertion was significantly higher among the midazolam group (21 seconds) than the dexmedetomidine group (19 seconds). A total of 93.8% of patients administered dexmedetomidine had excellent Muzi scores in comparison to midazolam group where only 13.8% patients had excellent Muzi scores (P < .001). CONCLUSION: Dexmedetomidine in a dose of 1 µg kg-1 as compared to midazolam (20 µg kg-1) produces better insertion characteristics for ProSeal laryngeal mask airway when used as adjuvant with propofol in terms of jaw opening, ease of insertion, coughing, gagging, patient movement, and laryngospasm.

5.
JCI Insight ; 8(5)2023 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-36883564

RESUMEN

Small cell lung cancer (SCLC) is a recalcitrant malignancy with limited treatment options. Bromodomain and extraterminal domain inhibitors (BETis) have shown promising preclinical activity in SCLC, but the broad sensitivity spectrum limits their clinical prospects. Here, we performed unbiased high-throughput drug combination screens to identify therapeutics that could augment the antitumor activities of BETis in SCLC. We found that multiple drugs targeting the PI-3K-AKT-mTOR pathway synergize with BETis, among which mTOR inhibitors (mTORis) show the highest synergy. Using various molecular subtypes of the xenograft models derived from patients with SCLC, we confirmed that mTOR inhibition potentiates the antitumor activities of BETis in vivo without substantially increasing toxicity. Furthermore, BETis induce apoptosis in both in vitro and in vivo SCLC models, and this antitumor effect is further amplified by combining mTOR inhibition. Mechanistically, BETis induce apoptosis in SCLC by activating the intrinsic apoptotic pathway. However, BET inhibition leads to RSK3 upregulation, which promotes survival by activating the TSC2-mTOR-p70S6K1-BAD cascade. mTORis block this protective signaling and augment the apoptosis induced by BET inhibition. Our findings reveal a critical role of RSK3 induction in tumor survival upon BET inhibition and warrant further evaluation of the combination of mTORis and BETis in patients with SCLC.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Inhibidores mTOR , Carcinoma Pulmonar de Células Pequeñas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/fisiología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Inhibidores mTOR/farmacología , Inhibidores mTOR/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Serina-Treonina Quinasas TOR
6.
Microbiol Res ; 271: 127340, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36889205

RESUMEN

Reduction in soil fertility and depletion of natural resources due to current intensive agricultural practices along with climate changes are the major constraints for crop productivity and global food security. Diverse microbial populations' inhabiting the soil and rhizosphere participate in biogeochemical cycling of nutrients and thereby, improve soil fertility and plant health, and reduce the adverse impact of synthetic fertilizers on the environment. Sulphur is 4th most common crucial macronutrient required by all organisms including plants, animals, humans and microorganisms. Effective strategies are required to enhance sulphur content in crops for minimizing adverse effects of sulphur deficiency on plants and humans. Various microorganisms are involved in sulphur cycling in soil through oxidation, reduction, mineralization, and immobilization, and volatalization processes of diverse sulphur compounds. Some microorganisms possess the unique ability to oxidize sulphur compounds into plant utilizable sulphate (SO42-) form. Considering the importance of sulphur as a nutrient for crops, many bacteria and fungi involved in sulphur cycling have been characterized from soil and rhizosphere. Some of these microbes have been found to positively affect plant growth and crop yield through multiple mechanisms including the enhanced mobilization of nutrients in soils (i.e., sulphate, phosphorus and nitrogen), production of growth-promoting hormones, inhibition of phytopathogens, protection against oxidative damage and mitigation of abiotic stresses. Application of these beneficial microbes as biofertilizers may reduce the conventional fertilizer application in soils. However, large-scale, well-designed, and long-term field trials are necessary to recommend the use of these microbes for increasing nutrient availability for growth and yield of crop plants. This review discusses the current knowledge regarding sulphur deficiency symptoms in plants, biogeochemical cycling of sulphur and inoculation effects of sulphur oxidizing microbes in improving plant biomass and crop yield in different crops.


Asunto(s)
Microbiología del Suelo , Suelo , Humanos , Suelo/química , Agricultura , Producción de Cultivos , Productos Agrícolas/microbiología , Azufre , Compuestos de Azufre , Fertilizantes/microbiología
7.
Indian J Crit Care Med ; 26(9): 1049-1051, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36213701

RESUMEN

Central pontine myelinolysis (CPM) classically occurs due to rapid rise in serum osmolarity. Most cases have been associated with a history of chronic alcohol abuse, malnutrition, diuretic abuse, and hyponatremia. The pathological process of CPM starts in the central pons near median raphe and spreads out "like a brush Fire" into the surrounding basis pontis. Extrapontine sites such as internal capsule, basal ganglia, cerebellum, and cerebrum can also be affected. We report a case of 60-year-old male with history of chronic alcoholism who presented to us with severe neurological deficits 10 days after his episode of severe hyponatremia. How to cite this article: Tiwari R, Kumari A. Central Pontine Myelinolysis: A Case Report. Indian J Crit Care Med 2022;26(9):1049-1051.

8.
Indian J Crit Care Med ; 26(2): 239-243, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35712740

RESUMEN

Bartter-like syndrome (BLS) is a constellation of biochemical abnormalities which include metabolic alkalosis, hypokalemia, hypocalcemia, hypomagnesemia with normal kidney function. BLS is a very rare syndrome and can be induced by certain diseases, antibiotics, diuretics, and antineoplastic drugs. Colistin is a polymicrobial bactericidal drug and currently re-emerged as the only salvation therapy against multidrug resistant bacilli especially in critically ill patients at intensive care units. Only an anecdotal case report of colistin-induced Bartter-like syndrome has been reported. We here report a case series of four critically ill patients who were on treatment with colistin and presented with serious metabolic disturbances. How to cite this article: Kumari A, Gupta P, Verma H, Kumar A, Thakur P, Sharma K. Colistin-induced Bartter-like Syndrome: Ponder before Treatment! Indian J Crit Care Med 2022;26(2):239-243.

9.
J Family Med Prim Care ; 11(3): 918-926, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35495806

RESUMEN

Background: Improving the quality of life of the geriatric population along with maintaining their health and promoting social participation still poses a major public health challenge in the twenty-first century. Hence, we planned to measure the quality of life (QOL) in each domain namely physical, psychological, social, and environmental using the world health organization quality of life brief version (WHO QOL-BREF) questionnaire and to assess the predictors of QOL among the elderly population. Methodology: A community-based cross-sectional study was conducted in Ormanjhi, Ranchi, Jharkhand for a period of 6 months. The study was carried out among 206 geriatric populations fulfilling the eligibility criteria. The data collected were entered in MS Excel and analyzed using SPSS version 20. The QOL scores were expressed in terms of mean and standard deviation, and the difference between mean scores was tested by using student t-test/analysis of variance (ANOVA). The predictor associated with QOL was done by multiple linear regression analysis. P value less than 0.05 was considered statistically significant. Results: A total of 206 geriatric people fulfilling the study criteria were enrolled during the study. The majority of the people were of the age between 60 and69 years (71.8%). Most of them 202 (98.1%) resided in rural areas, 108 (52.4%) of them were illiterate by education, and nearly half 102 (49.5%) depended on pension for livelihood. Nontribal ethnicity, backward category, illiteracy, low socio-economic status, nuclear family, elderly person having no own source of income, currently living alone, person having more co-morbidity, and less activities of daily living (ADL) score were significantly associated with low QOL score. Conclusion: Overall QOL was good to excellent in Ranchi, Jharkhand. We concluded that QOL is affected by many different factors.

10.
J Food Sci Technol ; 59(2): 745-753, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35153314

RESUMEN

Bacteriocin producing L. plantarum (ATCC 8014) was immobilized (MC) and freeze dried (FD) to conduct preliminary study on its potential in biopreservation of pineapple wine. Cell survival in both simulated gastric and intestinal juice was significantly better for MC and FD than free cells (FC).The antimicrobial activity and bacteriocin production of L. plantarum was detected against L. acidophilus, A. aceti, S. cerevisiae, E. coli, S. aureus and B. subtilis as indicator strains. Bacteriocin activity from MC revealed high zone of inhibition as compared to FC. In wine, bacteriocin found effective at 3.5 pH. Significant decrease of total soluble solids and sugar observed in wine treated with MC and FC. FD and MC treated wine was organolepticaly more accepted as compared to FC however, there was no significant difference in overall acceptability of pineapple wine under all treatments at P < 0.05.

11.
J Food Sci Technol ; 59(2): 754, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35185189

RESUMEN

[This corrects the article DOI: 10.1007/s13197-021-05069-6.].

12.
Anesth Essays Res ; 16(3): 326-330, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36620111

RESUMEN

Background: Video laryngoscopes (VL) assist in securing the airway faster and more accurately in difficult airways. However, data regarding its usefulness in patients with normal airways are sparse. Aim: We designed this study to compare the ease and success of endotracheal intubation between C-MAC and Macintosh direct laryngoscope (DL) in adult patients with no anticipated airway difficulty. Settings and Design: The design involves prospective randomized case - control study. Subjects and Methods: One hundred and twenty adult patients with predicted normal airway were randomized into two groups and were intubated using VL (C-MAC VL) and DL (Macintosh DL), respectively. The Cormack-Lehane (CL) grade, time taken for intubation, attempts taken (number), and need for laryngeal maneuvers or stylets were recorded and analyzed for statistical significance. Results: Thirty-eight patients in the DL group and 48 patients in the VL group had CL I view, 20 patients in the DL group and 16 patients in the VL group had CL II, and two patients in the DL group had CL III view. None of the patients in Group VL had CL III view. In seven out of 60 cases in the DL group, difficulty was experienced during insertion of the laryngoscope blade as compared to two cases out of 60 in the VL group. The mean time taken for intubation was lesser in Group DL (28.48 s) as compared to 39.3 s in Group VL. Nine patients in Group DL and 16 patients in Group VL required external laryngeal manipulation. Stylets were used, in seven patients in group DL and in 11 patients in group VL. Conclusions: In patients with a predicted normal airway, C-MAC provides a better glottic view compared to Macintosh DL. Time taken for intubation using the C-MAC video laryngoscope was more. However, success rates on the first attempt at endotracheal intubation and the number of intubation attempts with either laryngoscope were similar.

13.
J Basic Microbiol ; 62(9): 1064-1082, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34817092

RESUMEN

Astaxanthin is a ketocarotenoid, super antioxidant molecule. It has higher antioxidant activity than a range of carotenoids, thus has applications in cosmetics, aquaculture, nutraceuticals, therapeutics, and pharmaceuticals. Naturally, it is derived from Haematococcus pluvialis via a one-stage process or two-stage process. Natural astaxanthin significantly reduces oxidative and free-radical stress as compared to synthetic astaxanthin. The present review summarizes all the aspects of astaxanthin, including its structure, chemistry, bioavailability, and current production technology. Also, this paper gives a detailed mechanism for the potential role of astaxanthin as nutraceuticals for cardiovascular disease prevention, skin protection, antidiabetic and anticancer, cosmetic ingredient, natural food colorant, and feed supplement in poultry and aquaculture. Astaxanthin is one of the high-valued microalgae products of the future. However, due to some risks involved or not having adequate research in terms of long-term consumption, it is still yet to be explored by food industries. Although the cost of naturally derived astaxanthin is high, it accounts for only a 1% share in total astaxanthin available in the global market. Therefore, scientists are looking for ways to cut down the cost of natural astaxanthin to be made available to consumers.


Asunto(s)
Microalgas , Antioxidantes/uso terapéutico , Carotenoides , Xantófilas/uso terapéutico
14.
Curr Protein Pept Sci ; 22(9): 666-674, 2021 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-34751114

RESUMEN

The moonlighting protein, Prdx-6, exhibits peroxidase activity, phospholipase activity, and lysophosphatidylcholine acyltransferase (LPCAT) activity. Although it is ubiquitous in expression, its level is prominently high in the lung. Prdx-6 has been known to be an important enzyme for the maintenance of normal lung physiologies including, anti-oxidant defense, lung surfactant homeostasis, and cell signaling. Studies further unveiled that the altered activity (peroxidase or ai- PLA2) of this enzyme is linked with various lung pathologies or diseases. In the present article, we attempted to address the various pathophysiologies or disease conditions (like lung ischemia, hyperoxia, lung cancer, emphysema, and acute lung injury) wherein Prdx-6 is involved. The study implicates that Prdx-6 could be used as a common drug target for multiple lung diseases. Important future insights have also been incorporated.


Asunto(s)
Peroxiredoxina VI
15.
J Obstet Gynaecol India ; 71(1): 58-65, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33814800

RESUMEN

BACKGROUND: The aim of this study to determine maternal adiponectin and leptin levels as biomarkers of pre-eclampsia and compare adiponectin and leptin ratio. MATERIALS AND METHODS: This is a prospective study. The enrolled women were divided into two groups: first, study group (n = 60) comprised of women diagnosed with pre-eclampsia and second, control group (n = 60) comprised of age- and gestation-matched normotensive and nonproteinuric women. MAIN OUTCOME MEASURES: Maternal serum adiponectin and leptin levels and their ratio were compared in pre-eclamptic (study group) and normotensive (control group) women. RESULTS: Adiponectin levels were insignificantly higher in study group than control group. Leptin levels in study group were significantly higher than control group (p < 0.001). Adiponectin/leptin ratio was significantly lower in study group than controls (p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of serum leptin and serum adiponectin/leptin ratio as a biomarker of pre-eclampsia were 90%, 88.3%, 88.5%, 89.8% and 68.3%, 90%, 87.2%, 74%, respectively. Serum leptin levels and serum adiponectin/leptin ratio had cut-off point as 23.3 ng/ml and < 0.153, respectively. Accuracy of both serum leptin and adiponectin/leptin ratio was significant (p < 0.0001). CONCLUSION: Maternal leptin-level estimation should be integrated into the investigations for pre-eclampsia, and a cut-off level of > 23.3 ng/ml should be used as a biomarker for diagnosis. Adiponectin-leptin ratio should be considered as a biomarker for PE and should be determined in all cases of pre-eclampsia, and a cut-off of < 0.153 should be used for diagnosis.

16.
J Thorac Oncol ; 16(1): 89-103, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32927122

RESUMEN

INTRODUCTION: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM. METHODS: Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression. RESULTS: UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM. CONCLUSIONS: UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Línea Celular Tumoral , Proliferación Celular , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Mesotelioma/tratamiento farmacológico , Mesotelioma/genética , Ratones , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/genética , Ubiquitina-Proteína Ligasas
17.
ACS Appl Mater Interfaces ; 12(50): 56568-56578, 2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33283514

RESUMEN

Interface-driven multifunctional facets are gearing up in the field of science and technology. Here, we present the interface-activated resistive switching (RS), negative differential resistance, diode behavior, and ultraviolet (UV) light sensing in nanosheet-based hybrid devices. A hybrid device i.e., titanium dioxide nanosheet (TiO2-NS)/poly(dimercaptothiadiazole-triazine)[Poly(DMcT-CC)] is fabricated by spin coating Poly(DMcT-CC) polymer on hydrothermally as-grown TiO2-NS. The pristine devices of both materials show either small or no magnitude of RS, but the hybrid device shows highly enhanced RS of nearly four orders due to the formation of a p-n junction at the NS/polymer interface. The resistive random access memory feature appears to be more prominent in the hybrid device i.e., high and low current states are found to be stable in repetitive cycles since the interface acts as a trapping center for the carriers. The UV sensing ability of the hybrid device has been demonstrated by a threefold increment in a current at 60 mV. The impedance spectroscopy has been employed to show that the multifunctional features are directly associated to the NS/polymer interface, which deduce that the manipulation of such interfaces can pave the way for developing the hybrid structures.

18.
Nat Commun ; 11(1): 3547, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32669546

RESUMEN

Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) or Salmonella Typhimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils. Increased release of BM lactate preferentially promotes neutrophil mobilization by reducing endothelial VE-Cadherin expression, increasing BM vascular permeability via endothelial lactate-receptor GPR81 signaling. GPR81-/- mice mobilize reduced levels of neutrophils in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection.


Asunto(s)
Células de la Médula Ósea/inmunología , Ácido Láctico/metabolismo , Neutrófilos/inmunología , Receptores Acoplados a Proteínas G/metabolismo , Infecciones por Salmonella/inmunología , Animales , Médula Ósea/irrigación sanguínea , Células de la Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Endotelio Vascular/metabolismo , Femenino , Humanos , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Noqueados , Neutrófilos/metabolismo , Receptores Acoplados a Proteínas G/genética , Infecciones por Salmonella/microbiología , Salmonella typhimurium/inmunología , Transducción de Señal/inmunología
19.
J Food Sci Technol ; 57(7): 2472-2479, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32549597

RESUMEN

Diospyros kaki L., cv. Fuyu is a non-astringent seasonally available persimmon variety from New Zealand having short shelf life. Most of the current preservation techniques like pasteurization, spray drying etc. use high temperature for microbial inactivation, which results in quality reduction. In the present study, response surface methodology having Box-Behnken design used to explore the consequence of pressure (200-600 MPa), time (5-15 min) and temperature (20-45 °C) for controlling microbial load in fruit pulp. A mathematical model created to envision the responses, and the R2 value indicated that the established model proved highly accurate in the prediction of response. The optimization process advocated non-thermal minimal processing of persimmon pulp by high pressure processing at low temperature 20 °C, 400 MPa pressure for 5 min holding time for reducing total plate count and yeast mould count.

20.
Chem Commun (Camb) ; 56(19): 2949-2952, 2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32043102

RESUMEN

A degradative dimerisation of Morita-Baylis-Hillman ketones was observed in the presence of a primary diamine. The reaction proceeded swiftly to produce methylene-bridged 1,3-dicarbonyl compounds. A brief mechanistic investigation alluded to a retro-Mannich reaction as the key step of the transformation.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA