Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.113
Filtrar
1.
Development ; 150(22)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37870089

RESUMEN

Macroheterogeneity in follicle-stimulating hormone (FSH) ß-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is the abundant and more bioactive form in pituitaries of females under 35 years of age, whereas fully glycosylated FSH24 is less bioactive and increases with age. To investigate whether the shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, the direct effects of FSH glycoforms on folliculogenesis and oocyte quality were determined using an encapsulated in vitro mouse follicle growth system. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion and oocyte quality compared with FSH24 (10 ng/ml) treatment. FSH21 enhanced establishment of transzonal projections, gap junctions and cell-to-cell communication within 24 h in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. Our data indicate that FSH21 promotes folliculogenesis and oocyte quality in vitro by increasing cell-to-cell communication early in folliculogenesis, and that the shift in in vivo abundance from FSH21 to FSH24 with reproductive aging may contribute to the age-dependent decline in oocyte quality.


Asunto(s)
Hormona Folículo Estimulante , Oocitos , Femenino , Ratones , Animales , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/fisiología , Folículo Ovárico , Comunicación Celular , Estradiol/farmacología
2.
Am J Physiol Endocrinol Metab ; 326(5): E626-E639, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38536037

RESUMEN

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.


Asunto(s)
Metabolismo Energético , Estradiol , Hormona Folículo Estimulante , Ovariectomía , Ratas Wistar , Animales , Femenino , Metabolismo Energético/efectos de los fármacos , Ratas , Hormona Folículo Estimulante/metabolismo , Estradiol/farmacología , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Transcriptoma/efectos de los fármacos
3.
Biol Reprod ; 110(1): 198-210, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-37812459

RESUMEN

Di(2-ethylhexyl) phthalate and diisononyl phthalate are widely used as plasticizers in polyvinyl chloride products. Short-term exposures to phthalates affect hormone levels, ovarian follicle populations, and ovarian gene expression. However, limited data exist regarding the effects of long-term exposure to phthalates on reproductive functions. Thus, this study tested the hypothesis that short-term and long-term exposure to di(2-ethylhexyl) phthalate or diisononyl phthalate disrupts follicle dynamics, ovarian and pituitary gene expression, and hormone levels in female mice. Adult CD-1 female mice were exposed to vehicle, di(2-ethylhexyl) phthalate, or diisononyl phthalate (0.15 ppm, 1.5 ppm, or 1500 ppm) via the chow for 1 or 6 months. Short-term exposure to di(2-ethylhexyl) phthalate (0.15 ppm) and diisononyl phthalate (1.5 ppm) decreased serum follicle-stimulating hormone levels compared to control. Long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate (1500 ppm) increased the percentage of primordial follicles and decreased the percentages of preantral and antral follicles compared to control. Both phthalates increased follicle-stimulating hormone levels (di(2-ethylhexyl) phthalate at 1500 ppm; diisononyl phthalate at 1.5 ppm) and decreased luteinizing hormone levels (di(2-ethylhexyl) phthalate at 0.15 and 1.5 ppm; diisononyl phthalate at 1.5 ppm and 1500 ppm) compared to control. Furthermore, both phthalates altered the expression of pituitary gonadotropin subunit genes (Cga, Fshb, and Lhb) and a transcription factor (Nr5a1) that regulates gonadotropin synthesis. These data indicate that long-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate alters follicle growth dynamics in the ovary and the expression of gonadotropin subunit genes in the pituitary and consequently luteinizing hormone and follicle-stimulating hormone synthesis.


Asunto(s)
Dietilhexil Ftalato , Ácidos Ftálicos , Ratones , Animales , Femenino , Ácidos Ftálicos/toxicidad , Dietilhexil Ftalato/toxicidad , Folículo Ovárico/metabolismo , Hormona Folículo Estimulante/farmacología , Hormona Luteinizante/metabolismo
4.
Microb Pathog ; 191: 106677, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705217

RESUMEN

A novel endophytic Streptomyces griseorubens CIBA-NS1 was isolated from a salt marsh plant Salicornia sp. The antagonistic effect of S. griseorubens against Vibrio campbellii, was studied both in vitro and in vivo. The strain was validated for its endophytic nature and characterized through scanning electron microscopy, morphological and biochemical studies and 16SrDNA sequencing. The salinity tolerance experiment has shown that highest antibacterial activity was at 40‰ (16 ± 1.4 mm) and lowest was at 10 ‰ salinity (6.94 ± 0.51 mm). In vivo exclusion of Vibrio by S. griseorubens CIBA-NS1 was studied in Penaeus indicus post larvae and evaluated for its ability to improve growth and survival of P. indicus. After 20 days administration of S. griseorubens CIBA-NS1, shrimps were challenged with V. campbellii. The S. griseorubens CIBA-NS1 reduced Vibrio population in test group when compared to control, improved survival (60.5 ± 6.4%) and growth, as indicated by weight gain (1.8 ± 0.05g). In control group survival and growth were 48.4 ± 3.5% and 1.4 ± 0.03 g respectively. On challenge with V. campbellii, the S. griseorubens CIBA-NS1 administered group showed better survival (85.6 ± 10%) than positive control (64.3 ± 10%). The results suggested that S. griseorubens CIBA-NS1 is antagonistic to V. campbellii, reduce Vibrio population in the culture system and improve growth and survival. This is the first report on antagonistic activity of S. griseorubens isolated from salt marsh plant Salicornia sp, as a probiotic candidate to prevent V. campbellii infection in shrimps.


Asunto(s)
Chenopodiaceae , Endófitos , Probióticos , Streptomyces , Vibrio , Animales , Vibrio/efectos de los fármacos , Vibrio/fisiología , Chenopodiaceae/microbiología , Probióticos/farmacología , Endófitos/aislamiento & purificación , Endófitos/fisiología , Streptomyces/fisiología , Streptomyces/aislamiento & purificación , Streptomyces/genética , Penaeidae/microbiología , ARN Ribosómico 16S/genética , Antibiosis , Vibriosis/microbiología , Vibriosis/veterinaria , Vibriosis/prevención & control , Salinidad , Larva/microbiología , ADN Bacteriano/genética , Filogenia
5.
Chemistry ; 30(46): e202401623, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38825798

RESUMEN

Photoredox catalysis provides a green and sustainable alternative for C-H activation of organic molecules that eludes harsh conditions and use of transition metals. The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in infancy. A series of novel 21-thiaporphyrins (A2B2 and A3B type) were synthesized having carbazole/phenothiazine moieties at their meso-positions and screened as catalysts for C-N borylation and C-H arylation. This paper demonstrates the 21-thiaporphyrin catalyzed C-N borylation and het-arylation of anilines under visible light. The method utilizes only 0.1 mol % of 21-thiaporphyrin catalyst under blue light for the direct C-N borylation and het-arylation reactions. A variety of substituted anilines were used as source for expensive and unstable aryl diazonium salts in the reactions. The heterobiaryls and aryl boronic esters were obtained in decent yields (up to 88 %). Versatility of the 21-thiaporphyrin catalyst was tested by thiolation and selenylation of anilines under similar conditions. Mechanistic insight was obtained from DFT studies, suggesting that 21-thiaporphyrin undergo an oxidative quenching pathway. The photoredox process catalyzed by 21-thiaporphyrins offers a mild, efficient and metal-free alternative for the formation of C-C, C-S, and C-Se bonds in aryl compounds; it can also be extended to borylation reaction.

6.
Phys Chem Chem Phys ; 26(14): 11140-11149, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38530754

RESUMEN

In recent years, hydrogen (H2) has become the most sought-after sustainable energy carrier by virtue of its high energy content and carbon-free emission. The practical implementation of hydrogen as an alternative fuel calls for an efficient and secure storage medium. Within this framework, we have investigated Li-grafted Si-doped γ-graphyne for H2 storage applications by implementing the cutting-edge density functional theory (DFT). A dynamically and thermally stable Si-doped γ-graphyne (SiG) monolayer is functionalized with Li metal atoms that augmented the hydrogen binding strength of the nanolayer by almost three times, owing to the polarization effect of the Li atoms. The Li metal atoms get adsorbed over the monolayer, allowing a binding energy of -2.73 eV that is greater than the Li cohesive energy (-1.63 eV), which eliminates the metal-metal clustering probability. The reliability of the Li-functionalized SiG monolayer (Li8SiG) at elevated temperature has been further substantiated by performing and analyzing ab initio molecular dynamics (AIMD) simulations at 400 K. It is noteworthy that a total of four H2 molecules are held up by each Li atom with an average adsorption energy of -0.32 eV and a maximum gravimetric capacity of 8.48 wt%, which remarkably follows the US-DOE parameters. Partial density of states and Hirshfeld charge analysis are utilized to recognize the interaction channel which reveals the Kubas and Niu-Rao-Jena-like bonding among the metal atoms and loaded hydrogen molecules. The hydrogen occupancy calculated at different temperatures and pressures indicates that hydrogen molecules can be reversibly stored over the Li8SiG system, and it is noted that adsorbed H2 begins to desorb at 280 K, with complete desorption at 400 K and 20 atm (or lower). AIMD simulations are further performed to authenticate the H2 desorption at various temperatures, which agrees well with the occupation number analysis. All the outcomes advocate for efficient reversible hydrogen storage over the proposed host material.

7.
Phys Chem Chem Phys ; 26(9): 7482-7491, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38354053

RESUMEN

A new four dimensional (4D) ab initio potential energy surface (PES) is generated for the collision of C4(3Σg-) with H2(1Σg), considering both molecules as rigid rotors. A supervised neural network model is created to augment the ab initio PES and to get the missing data points. Furthermore, space fixed expansion of the augmented PES is carried out using a least squares fit over two spherical harmonics terms, resulting in radial coefficients (λ1, λ2, and λ). The centre of symmetry in both C4 and H2 forces λ1 and λ2 to have even values, respectively. Moreover, the rotational states of C4 are only populated by odd levels due to its ground state triplet symmetry and the nuclear spin (I = 0) of 12C. The cross-sections and rate coefficients with para and ortho H2 partners are studied for various odd state transitions, where the rate coefficients of the ortho are 10-20% higher than those of the latter. The de-excitation rates obtained by the para H2 collisions are also compared to those of He and are found to be ∼1.7-2.8 times the He rates, across various order transitions. The simple scaling of He rates using a factor of 1.38 proves insufficient to describe para H2 rates. Therefore, these results show the importance of explicitly studying H2 as an important colliding partner, governing the kinetics of various rotational processes in the interstellar space.

8.
J Pharm Pharm Sci ; 27: 12721, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939359

RESUMEN

Antimicrobial resistance (AMR) is a global public health crisis that impedes the therapeutic effectiveness of available antimicrobial agents. Due to the high burden of infectious diseases and limited resources, especially trained healthcare professionals, low- and middle-income countries (LMICs) are particularly susceptible to the detrimental effects of AMR. Sometimes, as the first and last point of contact for patients seeking treatment for infections, community pharmacists can play a pivotal role in the stewardship required for AMR. This review aims to highlight the contributions made by community pharmacists in LMICs as AMR stewards. The review considers the challenges from the perspectives of limited resources, inadequate training, a lack of policies and regulations, and issues related to patient behavior. Community pharmacists in LMICs could optimize their advocacy contributions by focusing on One Health AMR stewardship. Transformational and actionable patient and population-centric antimicrobial stewardship (AMS) is feasible with the synergy of policymakers and other healthcare providers in the implementation of AMS policies and programs that support community pharmacists in their efforts to promote rational antimicrobial use.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Países en Desarrollo , Farmacéuticos , Humanos , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Servicios Comunitarios de Farmacia/organización & administración , Rol Profesional
9.
J Chem Phys ; 161(6)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39120031

RESUMEN

The rotational dynamics of isocyanogen (CNCN) is studied for its collision with para (p-) and ortho (o-) hydrogen (H2) in the temperature range of 1-100 K. These temperatures correspond to the cold dense molecular clouds in the interstellar medium where molecular hydrogen is the primary collider. An ab initio 4D potential energy surface (PES) is constructed keeping the two molecules under rigid rotor approximation. The PES is generated using the CCSD(T)-F12b/AVTZ level of theory. The 4D PES is further fitted into a neural network (NN) model, which can augment the surface and account for missing data points within spectroscopic accuracy. This NN-fitted PES is then expanded over a bispherical harmonics function to get radial terms, which are expressed into analytic functions. Thereafter, the cross sections (σ) are computed for rotational transitions of CNCN (j → j') using the close-coupling and centrifugal sudden methods for both p-H2 (jc = 0) and o-H2 (jc = 1) collision till 194 cm-1. In addition, p-H2 (jc = 0, 2) cross sections are also computed using the centrifugal sudden approximation method. The collisional rates are achieved by taking the Boltzmann distribution of σ over the translational energy of H2 till 100 K. Finally, the CNCN-H2 rates are compared to CNCN-He and NCCN-H2 collisional rates. Comparing even and odd transitions for the CNCN-H2 rates show a propensity toward higher rates for even transitions especially for o-H2 collisions considering low-order transitions.

10.
J Sep Sci ; 47(14): e2400141, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39054594

RESUMEN

Hydroxyapatite (HAp) is a calcium phosphate ceramic, widely used as a matrix for protein chromatography. The crystal structure of HAp is amenable to a wide range of substitutions, thus allowing for the alteration of its properties. In this study, nickel-ion substituted HAp (NiSHAp) was synthesized using a wet-precipitation method, followed by spray drying. This resulted in the structural incorporation of nickel ions within well-defined microspheres, which were suitable for chromatographic applications. The chromatographic experiments were conducted with NiSHAp and compared with spray-dried hydroxyapatite (SHAp) matrices. Protein purification experiments were conducted using refolded recombinant L-asparaginase (L-Asp), which was produced as inclusion bodies in Escherichia coli. The results showed that NiSHAp effectively adsorbed L-Asp, which was selectively eluted using a phosphate buffer, surpassing the efficiency of imidazole-based elution. In contrast, SHAp showed weaker binding and lower selectivity. The significance of this study lies in developing a scalable NiSHAp matrix for protein purification, especially for large-scale applications. The NiSHAp matrix offers a cost-effective alternative to commercial immobilized metal affinity chromatography (IMAC) adsorbents, especially for purifying His-tagged proteins. This innovative approach exhibits the advantages of mixed-mode chromatography by combining the properties of hydroxyapatite and IMAC in a single matrix, with the potential of improved industrial-scale protein purification.


Asunto(s)
Cromatografía de Afinidad , Durapatita , Níquel , Proteínas Recombinantes , Durapatita/química , Cromatografía de Afinidad/métodos , Níquel/química , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Escherichia coli/química , Adsorción
11.
Community Ment Health J ; 60(1): 131-147, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37679654

RESUMEN

The use of Lay Mental Health Workers (LMHWs) to tackle the treatment gap in low-resource settings is well established, and although they often receive training, the potential of proper supervision to improve outcomes remains untapped. Indeed, given the strain on expert resources, peer-supervision models based on supervisors' seniority of work experience have significant potential especially in relation to community knowledge and embedding of LMHWs. This study summarizes the evaluation of a pilot program for peer supervision on the basis of Social Cognitive Theories of Self-Efficacy for LMHWs in Kerala, India. Two experienced LMHWs worked as supervisors for a total of 12 LMHWs over the course of a year. These participants were subsequently interviewed to analyze their experiences in order to evaluate the potential of peer supervision and distil relevant information to improve future training of LMHWs. The findings include improved performance and emotional support for the participants.


Asunto(s)
Agentes Comunitarios de Salud , Salud Mental , Humanos , India , Agentes Comunitarios de Salud/educación
12.
J Environ Manage ; 354: 120477, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38417362

RESUMEN

The Indian coastal waters are stressed due to a multitude of factors, such as the discharge of industrial effluents, urbanization (municipal sewage), agricultural runoff, and river discharge. The coastal waters along the eastern and western seaboard of India exhibit contrasting characteristics in terms of seasonality, the magnitude of river influx, circulation pattern, and degree of anthropogenic activity. Therefore, understanding these processes and forecasting their occurrence is highly necessary to secure the health of coastal waters, habitats, marine resources, and the safety of tourists. This article introduces an integrated buoy-satellite based Water Quality Nowcasting System (WQNS) to address the unique challenges of water quality monitoring in Indian coastal waters and to boost the regional blue economy. The Indian National Centre for Ocean Information Services (INCOIS) has launched a first-of-its-kind WQNS, and positioned the buoys at two important locations along the east (Visakhapatnam) and west (Kochi) coast of India, covering a range of environmental conditions and tourist-intensive zones. These buoys are equipped with different physical-biogeochemical sensors, data telemetry systems, and integration with satellite-based observations for real-time data transmission to land. The sensors onboard these buoys continuously measure 22 water quality parameters, including surface current (speed and direction), salinity, temperature, pH, dissolved oxygen, phycocyanin, phycoerythrin, Coloured Dissolved Organic Matter, chlorophyll-a, turbidity, dissolved methane, hydrocarbon (crude and refined), scattering, pCO2 (water and air), and inorganic macronutrients (nitrite, nitrate, ammonium, phosphate, silicate). This real-time data is transmitted to a central processing facility at INCOIS, and after necessary quality control, the data is disseminated through the INCOIS website. Preliminary results from the WQNS show promising outcomes, including the short-term changes in the water column oxic and hypoxic regimes within a day in coastal waters off Kochi during the monsoon period, whereas effluxing of high levels of CO2 into the atmosphere associated with the mixing of water, driven by local depression in the coastal waters off Visakhapatnam. The system has demonstrated its ability to detect changes in the water column properties due to episodic events and mesoscale processes. Additionally, it offers valuable data for research, management, and policy development related to coastal water quality.


Asunto(s)
Ecosistema , Calidad del Agua , India , Océanos y Mares , Naciones Unidas , Monitoreo del Ambiente , Agua de Mar/química
13.
Angew Chem Int Ed Engl ; : e202411133, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39091222

RESUMEN

The sulfane sulfur pool, comprised of persulfide (RS-SH) and polysulfide (RS-SnH) derived from hydrogen sulfide (H2S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial sulfane sulfur (MSS) remain largely uncharacterized as compared with their cytosolic counterparts, cytosolic sulfane sulfur (CSS). To investigate this, we designed a novel artificial substrate for mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST), a key enzyme involved in MSS biosynthesis. Using cells expressing a mitochondrion-localized persulfide biosensor, we demonstrate this tool's ability to selectively enhance MSS. While H2S was previously known to suppress human immunodeficiency virus (HIV-1), we found that MSS profoundly affected the HIV-1 life cycle, mediating viral reactivation from latency. Additionally, we provide evidence for the role of the host's mitochondrial redox state, membrane potential, apoptosis, and respiration rates in managing HIV-1 latency and reactivation. Together, dynamic fluctuations in the MSS pool have a significant and possibly conflicting effect on HIV-1 viral latency. The precision tools developed herein allow for orthogonal generation of persulfide within both mitochondria and the cytosol and will be useful in interrogating disease biology.

14.
Indian J Crit Care Med ; 28(Suppl 2): S279-S287, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39234226

RESUMEN

How to cite this article: Ramakrishnan N, Abraham BK, Barokar R, Chanchalani G, Jagathkar G, Shetty RM, et al. Post-ICU Care: Why, What, When and How? ISCCM Position Statement. Indian J Crit Care Med 2024;28(S2):S279-S287.

15.
Tumour Biol ; 45(1): 31-54, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37574746

RESUMEN

BACKGROUND: Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs. OBJECTIVE: To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients. METHODS: Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry. RESULTS: Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential. CONCLUSIONS: Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Galectina 3/genética , Galectina 3/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Vimentina/genética , Vimentina/metabolismo
16.
Chemistry ; 29(41): e202300393, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37155600

RESUMEN

Finding an ideal bioorthogonal reaction that responds to a wide range of biological queries and applications is of great interest in biomedical applications. Rapid diazaborine (DAB) formation in water by the reactions of ortho-carbonyl phenylboronic acid with α-nucleophiles is an attractive conjugation module. Nevertheless, these conjugation reactions demand to satisfy stringent criteria for bioorthogonal applications. Here we show that widely used sulfonyl hydrazide (SHz) offers a stable DAB conjugate by combining with ortho-carbonyl phenylboronic acid at physiological pH, competent for an optimal biorthogonal reaction. Remarkably, the reaction conversion is quantitative and rapid (k2 >103  M-1 s-1 ) at low micromolar concentrations, and it preserves comparable efficacy in a complex biological milieu. DFT calculations support that SHz facilitates DAB formation via the most stable hydrazone intermediate and the lowest energy transition state compared to other biocompatible α-nucleophiles. This conjugation is extremely efficient on living cell surfaces, enabling compelling pretargeted imaging and peptide delivery. We anticipate this work will permit addressing a wide range of cell biology queries and drug discovery platforms exploiting commercially available sulfonyl hydrazide fluorophores and derivatives.


Asunto(s)
Ácidos Borónicos , Química Clic , Química Clic/métodos , Colorantes Fluorescentes , Hidrazonas
17.
Phys Chem Chem Phys ; 25(36): 24904-24911, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37681247

RESUMEN

The objective of this study is to enhance our understanding of the existence of molecules in interstellar space by determining the collisional rate coefficients with the most prevalent species. The study examines the impact of para-H2 collisions, specifically when it is in its ground vibrational state with a nuclear spin of para-H2, i.e., jp = 0, on causing the rotational deexcitation of the diisocyanogen (CNNC) molecule. These scattering data are obtained as a result of spherically averaging a four-dimensional potential energy surface (4DPES) over the H2 orientations. Using the CCSD(T)-F12a approach and aug-cc-pVTZ basis sets, the ab initio 4DPES for the CNNC-H2 van der Waals system is calculated. The CNNC-para-H2 4DPES attains a global minimum of 221.38 cm-1 at the CNNC and H2 center of mass distance (R) of 3.1 Å. The method of close coupling calculations is employed for the purpose of calculating the cross-sectional data of CNNC with para-H2 (jp = 0), for total energies up to 1000 cm-1. Rate coefficients are computed over the temperature range of 1 K to 100 K. Propensity suggests that even Δj transitions are strongly preferred. The rate coefficients for CNNC-H2 are determined to be 0.90-2.95 times those of CNNC-He, which implies it is not reliable to estimate the H2 rate coefficients by multiplying the rate coefficients for CNNC-He collision with a scaling factor of 1.38.

18.
Phys Chem Chem Phys ; 25(18): 12934-12942, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37098834

RESUMEN

Boron-pnictogen (BX; X = N, P, As, Sb) materials, in most cases, share structural characteristics with the aesthetically pleasing architectures of carbon allotropes. Recently, a two-dimensional (2D) metallic carbon allotrope (biphenylene) has been synthesized using experimental methods. In the present study, we have examined the structural stabilities, mechanical properties, and electronic fingerprints of biphenylene analogs of boron-pnictogen (bp-BX) monolayers using state-of-the-art electronic structure theory. We have validated the dynamical stability using phonon band dispersion analysis and thermal stabilities using ab initio molecular dynamics studies. The bp-BX monolayers exhibit a positive (bp-BN) and negative (bp-BP, bp-BAs, bp-BSb) Poisson's ratio with anisotropic mechanical properties in the 2D plane. Electronic structure studies unveil that the bp-BX monolayers show semiconducting properties with an energy gap of 4.50, 1.30, 2.28 and 1.24 eV for X = N, P, As and Sb, respectively. Computed band edge positions, lighter charge carriers and optimally separated hole and electron regions indicate that the bp-BX monolayers can serve as potential candidates for the metal-free water dissociation reaction using photocatalysis.

19.
Nature ; 546(7656): 107-112, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28538730

RESUMEN

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.


Asunto(s)
Tejido Adiposo/metabolismo , Adiposidad , Hormona Folículo Estimulante de Subunidad beta/antagonistas & inhibidores , Termogénesis , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo Beige/efectos de los fármacos , Tejido Adiposo Beige/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adiposidad/efectos de los fármacos , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Dieta Alta en Grasa/efectos adversos , Femenino , Hormona Folículo Estimulante de Subunidad beta/inmunología , Haploinsuficiencia , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/prevención & control , Osteoporosis/tratamiento farmacológico , Ovariectomía , Consumo de Oxígeno/efectos de los fármacos , Receptores de HFE/antagonistas & inhibidores , Receptores de HFE/genética , Receptores de HFE/metabolismo , Termogénesis/efectos de los fármacos , Proteína Desacopladora 1/biosíntesis
20.
Environ Res ; 238(Pt 2): 117193, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37758116

RESUMEN

Carbaryl and carbofuran are the carbamate pesticides which have been widely used worldwide to control insects in crops and house. If the pesticides entered in to the food products and drinking water, they could cause serious health effects in humans. Therefore, the development of a rapid, simple, sensitive and selective analytical device for on-site detection of carbamates is crucial to evaluate food and environmental samples. Recently, semiconducting single-walled carbon nanotube-based field effect transistors (s-SWCNT/FETs) have shown several advantages such as high carrier mobility, good on/off ratio, quasi ballistic electron transport, label-free detection and real-time response. Herein, cobalt ferrite (CFO) nanoparticles decorated s-SWCNTs have been prepared and used to bridge the source and drain electrodes. As-prepared CFO/s-SWCNT/FET had been used for the non-enzymatic detection of carbaryl and carbofuran. When used as a sensing platform, the CFO/s-SWCNT hybrid film exhibited high sensitivity, and selectivity with a wide linear range of detection from 10 to 100 fMand the lowest limit of detections for carbaryl (0.11 fM) and carbofuran (0.07 fM) were estimated. This sensor was also used to detect carbaryl in tomato and cabbage samples, which confirmed its practical acceptance. Such performance may be attributed to the oxidation of carbamates by potent catalytic activity of CFO, which led to the changes in the charge transfer reaction on the s-SWCNTs/FET conduction channel. This work presents a novel CFO/s-SWCNT based sensing system which could be used to quantify pesticide residues in food samples.


Asunto(s)
Carbofurano , Nanotubos de Carbono , Plaguicidas , Humanos , Carbaril , Nanotubos de Carbono/química , Carbamatos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA