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1.
Artículo en Inglés | MEDLINE | ID: mdl-38321901

RESUMEN

Lung cancer is the second deadliest disease in the world. A major portion of deaths related to cancer are due to lung cancer in both males and females. Interestingly, unbelievable advances have occurred in recent years through the use of nanotechnology and development in both the diagnosis and treatment of lung cancer. Due to their in vivo stability, the nanotechnology-based pharmacological system gained huge attractiveness, solubility, absorption from the intestine, pharmacological effectiveness, etc. of various anticancer agents. However, this field needs to be utilized more to get maximum results in the treatment of lung cancer, along with wider context medicines. In the present review, authors have tried to concentrate their attention on lung cancer`s difficulties along with the current pharmacological and diagnostic situation, and current advancements in approaches based on nanotechnology for the treatment and diagnosis of lung cancer. While nanotechnology offers these promising avenues for lung cancer diagnosis and treatment, it is important to acknowledge the need for careful evaluation of safety, efficacy, and regulatory approval. With continued research and development, nanotechnology holds tremendous potential to revolutionize the management of lung cancer and improve patient outcomes. The review also highlights the involvement of endocrine systems, especially estrogen in lung cancer proliferation. Some of the recent clinical trials and patents on nanoparticle-based formulations that have applications in the treatment and diagnosis of lung cancer are also discussed.

2.
Ecotoxicol Environ Saf ; 269: 115783, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38061081

RESUMEN

Symbiotic interactions play a vital role in maintaining the phosphate (Pi) nutrient status of host plants and providing resilience during biotic and abiotic stresses. Serendipita indica, a mycorrhiza-like fungus, supports plant growth by transporting Pi to the plant. Despite the competitive behaviour of arsenate (AsV) with Pi, the association with S. indica promotes plant growth under arsenic (As) stress by reducing As bioavailability through adsorption, accumulation, and precipitation within the fungus. However, the capacity of S. indica to enhance Pi accumulation and utilization under As stress remains unexplored. Axenic studies revealed that As supply significantly reduces intracellular ACPase activity in S. indica, while extracellular ACPase remains unaffected. Further investigations using Native PAGE and gene expression studies confirmed that intracellular ACPase (isoform2) is sensitive to As, whereas extracellular ACPase (isoform1) is As-insensitive. Biochemical analysis showed that ACPase (isoform1) has a Km of 0.5977 µM and Vmax of 0.1945 Unit/min. In hydroponically cultured tomato seedlings, simultaneous inoculation of S. indica with As on the 14thday after seed germination led to hyper-colonization, increased root/shoot length, biomass, and induction of ACPase expression and secretion under As stress. Arsenic-treated S. indica colonized groups (13.33 µM As+Si and 26.67 µM As+Si) exhibited 8.28-19.14 and 1.71-3.45-fold activation of ACPase in both rhizospheric media and root samples, respectively, thereby enhancing Pi availability in the surrounding medium under As stress. Moreover, S. indica (13.33 µM As+Si and 26.67 µM As+Si) significantly improved Pi accumulation in roots by 7.26 and 9.46 times and in shoots by 4.36 and 8.85 times compared to the control. Additionally, S. indica induced the expression of SiPT under As stress, further improving Pi mobilization. Notably, fungal colonization also restricted As mobilization from the hydroponic medium to the shoot, with a higher amount of As (191.01 ppm As in the 26.67 µM As+Si group) accumulating in the plant's roots. The study demonstrates the performance of S. indica under As stress in enhancing Pi mobilization while limiting As uptake in the host plant. These findings provide the first evidence of the As-Pi interaction in the AM-like fungus S. indica, indicating reduced As uptake and regulation of PHO genes (ACPase and SiPT genes) to increase Pi acquisition. These data also lay the foundation for the rational use of S. indica in agricultural practices.


Asunto(s)
Fosfatasa Ácida , Arsénico , Basidiomycota , Micorrizas , Arsénico/toxicidad , Arsénico/metabolismo , Basidiomycota/metabolismo , Micorrizas/fisiología , Fosfatos/farmacología , Fosfatos/metabolismo , Raíces de Plantas/metabolismo , Fosfatasa Ácida/metabolismo , Fosfatasa Ácida/farmacología
3.
ACS Omega ; 8(12): 11065-11075, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37008120

RESUMEN

The presence of antibiotics in the aqueous environment has been a serious concern primarily due to the development of antimicrobial resistance (AMR) in diverse microbial populations. To overcome the rising AMR concerns, antibiotic decontamination of the environmental matrices may play a vital role. The present study investigates the use of zinc-activated ginger-waste derived biochar for the removal of six antibiotics belonging to three different classes, viz., ß-lactams, fluoroquinolones, and tetracyclines from the water matrix. The adsorption capacities of activated ginger biochar (AGB) for the concurrent removal of the tested antibiotics were investigated at different contact times, temperatures, pH values, and initial concentrations of the adsorbate and adsorbent doses. AGB demonstrated high adsorption capacities of 5.00, 17.42, 9.66, 9.24, 7.15, and 5.40 mg/g for amoxicillin, oxacillin, ciprofloxacin, enrofloxacin, chlortetracycline, and doxycycline, respectively. Further, among the employed isotherm models, the Langmuir model fitted well for all the antibiotics except oxacillin. The kinetic data of the adsorption experiments followed the pseudo-second order kinetics suggesting chemisorption as the preferred adsorption mechanism. Adsorption studies at different temperatures were conducted to obtain the thermodynamic characteristics suggesting a spontaneous exothermic adsorption phenomenon. AGB being a waste-derived cost-effective material shows promising antibiotic decontamination from the water environment.

4.
Front Microbiol ; 13: 828430, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35387085

RESUMEN

Human immunodeficiency virus type 1 (HIV-1) has RNA genome and depends on host cellular machinery for most of its activities. Host cellular proteins modulate the expression and activity of viral proteins to combat the virus. HIV-1 proteins are known to regulate each other for the benefit of virus by exploiting these modulations. Here, we report that HIV-1 Vif increases the levels of Tat via AKT signaling pathway. We show that HIV-1 Vif activates AKT signaling pathway by inducing phosphorylation of AKT. Mdm2, downstream target of AKT signaling, increases the levels of Tat protein in ubiquitin-dependent manner by inducing Ubiquitin Specific Protease 17 (USP17), which is a deubiquitinase and stabilizes Tat protein. Thus, HIV-1 proteins exploit AKT signaling pathway to promote viral replication.

5.
J Mol Biol ; 434(5): 167403, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-34914966

RESUMEN

COVID-19 caused by SARS-CoV-2 is the latest pandemic which has thrown the world into an unprecedented social and economic uncertainties along with huge loss to humanity. Identification of the host factors regulating the replication of SARS-CoV-2 in human host may help in the development of novel anti-viral therapies to combat the viral infection and spread. Recently, some research groups used genome-wide CRISPR/Cas screening to identify the host factors critical for the SARS-CoV-2 replication and infection. A comparative analysis of these significant host factors (p < 0.05) identified fifteen proteins common in these studies. Apart from ACE2 (receptor for SARS-CoV-2 attachment), other common host factors were CSNK2B, GDI2, SLC35B2, DDX51, VPS26A, ARPP-19, C1QTNF7, ALG6, LIMA1, COG3, COG8, BCOR, LRRN2 and TLR9. Additionally, viral interactome of these host factors revealed that many of them were associated with several SARS-CoV-2 proteins as well. Interestingly, some of these host factors have already been shown to be critical for the pathogenesis of other viruses suggesting their crucial role in virus-host interactions. Here, we review the functions of these host factors and their role in other diseases with special emphasis on viral diseases.


Asunto(s)
COVID-19/virología , Interacciones Microbiota-Huesped , Factores Celulares Derivados del Huésped/metabolismo , Pandemias , SARS-CoV-2/fisiología , COVID-19/epidemiología , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Factores Celulares Derivados del Huésped/genética , Humanos , SARS-CoV-2/genética
6.
J Family Med Prim Care ; 11(10): 6250-6254, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36618149

RESUMEN

Background: People who inject drugs are vastly over-represented, often accounting for 50% of prison inmates, so, the transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV) and tuberculosis (TB) is a serious problem in many prison systems. The prevalence of HCV infection is so disproportionately high in the correctional population that one in four detainees worldwide is living with HCV and the story is similar for HIV. Objective: The objective of the study is to find the prevalence of HIV, HCV and dual HIV-HCV infection in the prison inmates. Materials and Methods: A sample of 1569 jail inmates was assessed, after obtaining formal approval from the ethical committee for assessment of the medical record of subjects, to know sero-positivity for HIV and HCV. The data generated is then analysed. Results: The results show a very high point prevalence of HIV (10.0%) and HCV (31.6%) in the jail inmates, which is 40 and 30 times higher, respectively, as compared to the national average. A staggering 8.5% of the inmates were found to be positive for both viruses. The sero-prevalence for mono-infection for HCV (23.1%) is found to be significantly higher compared to HIV (1.5%). The infection rate of HCV was found to be three times higher compared to HIV. Conclusions: Substantially high prevalence of HIV, HCV and dual HIV-HCV infection exists in the prison inmates. Data suggests high virulence for HCV compared to HIV, as both viruses have common routes of transmission. There is an urgent need to keep a constant check on the intravenous drug usage (IDU) in the prisons that is linked to the common transmission of both these blood-borne viruses.

7.
Emerg Microbes Infect ; 8(1): 1626-1635, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31711408

RESUMEN

Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity. Earlier studies have established the fact that dengue virus (DENV) infection causes haemorrhagic fever and shock syndrome, but it is not directly responsible for exhibiting these clinical symptoms. It is noteworthy that clinically, vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines. The onset of hyperpermeability in severe cases of dengue disease takes place around the time of defervescence and after clearance of viraemia. Extracellular vesicles are known to carry biological information (mRNA, miRNA, transcription factors) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals. In dengue virus infection, the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines. Here, we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special focus on the role of secreted extracellular vesicles.


Asunto(s)
Virus del Dengue/fisiología , Exosomas/virología , Dengue Grave/virología , Animales , Citocinas/genética , Citocinas/metabolismo , Virus del Dengue/genética , Exosomas/genética , Exosomas/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Dengue Grave/genética , Dengue Grave/metabolismo
8.
Environ Sci Pollut Res Int ; 26(31): 32175-32188, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31494845

RESUMEN

Arsenic contamination in drinking water is a matter of concern for many countries. An efficient and low-cost solution for this hazard is essentially needed on urgent basis. Therefore, in this study, banana pith (an agricultural waste) was used for biochar production and later it was modified with iron and applied for arsenic adsorption from aqueous solution. Produced biochar was characterized for proximate, ultimate, and surface analyses. Interestingly, after iron impregnation, the surface area of biochar increased (31.59 m2/g) by nearly 8 times. Morphological analysis showed that iron particles firmly held within the pores after impregnation. Arsenate (As(V)) adsorption behavior of iron-impregnated banana pith biochar was evaluated through a batch study by considering various parameters like dose, concentration, pH, temperature, and competing anions. Compared to impregnated biochar, raw biomass and its biochar showed a lesser affinity for arsenate in aqueous solution. The adsorption isotherm of As(V) on banana pith biochar was covered in the temperature range of 298 to 318 K, and kinetic data of adsorption was experimentally generated at 298 K. Langmuir model for the sorption isotherms and pseudo-second-order kinetic model for the sorption kinetics represented the experimental data. The thermodynamic study showed negative Gibb's free energy (- 46.88 kJ/mol at 298 K, - 48.58 kJ/mol at 308 K, - 50.73 kJ/mol at 318 K) that suggested spontaneity of the adsorption process. Negative enthalpy (ΔH° = - 10.55 kJ/mol) showed exothermic nature of adsorption of arsenic, while negative entropy (ΔS° = 0.123 kJ/mol.K) suggested enthalpy-driven adsorption process. Mechanism of arsenic adsorption onto iron-impregnated banana pith biochar has also been discussed in detail. Based on the experimental observation, a predictive model for arsenate removal has been developed in this study. The findings of the present study elucidated that iron-impregnated banana pith biochar can be used as a low-cost adsorbing material for As(V) from aqueous solutions.


Asunto(s)
Arseniatos/química , Arsénico/análisis , Carbón Orgánico/análisis , Hierro/química , Adsorción , Arsénico/química , Biomasa , Carbón Orgánico/química , Cinética , Análisis de Regresión , Temperatura , Termodinámica , Agua
9.
Front Microbiol ; 10: 114, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30766526

RESUMEN

Human Immunodeficiency Virus-1 (HIV-1) is known to induce the expression of SOCS3 which is a negative feed-back regulator of inflammatory responses. Here, we demonstrate that reactivation of latent HIV-1 leads to degradation of SOCS3 at early time points. Interestingly, SOCS3 degradation following transfection of HIV-1 RNA as well as polyIC in THP-1 cells further confirmed the role of viral RNA signaling in SOCS3 biology. Degradation of SOCS3 contributes toward viral RNA induced inflammatory responses. NF-κB signaling is also induced upon HIV-1 infection which leads to the production of pro-inflammatory cytokines to control the viral spread. Further investigations revealed that SOCS3 inhibits the expression and activity of p65 by interacting with it and inducing its ubiquitin-dependent proteasomal degradation. SH2 domain was critical for SOCS3-p65 interaction and p65 degradation. We also found that expression of SOCS3 promotes HIV-1 replication. Thus, HIV-1 downregulates SOCS3 in early phase of infection to promote inflammatory responses for large production of activated cells which are suitable for viral spread and induces SOCS3 later on to limit inflammatory responses and ensure viral survival.

10.
Front Microbiol ; 9: 2738, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30524389

RESUMEN

Proteasomal degradation pathways play a central role in regulating a variety of protein functions by controlling not only their turnover but also the physiological behavior of the cell. This makes it an attractive target for the pathogens, especially viruses which rely on the host cellular machinery for their propagation and pathogenesis. Viruses have evolutionarily developed various strategies to manipulate the host proteasomal machinery thereby creating a cellular environment favorable for their own survival and replication. Human immunodeficiency virus-1 (HIV-1) is one of the most dreadful viruses which has rapidly spread throughout the world and caused high mortality due to its high evolution rate. Here, we review the various mechanisms adopted by HIV-1 to exploit the cellular proteasomal machinery in order to escape the host restriction factors and components of host immune system for supporting its own multiplication, and successfully created an infection.

11.
Sci Rep ; 8(1): 14496, 2018 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-30262819

RESUMEN

Despite the high success rate, antiretroviral therapy does not cure the disease completely due to presence of latent viral reservoirs. Although several studies have addressed this issue earlier, the role of serum starvation/deprivation in HIV-1 latency has not been studied. So, we investigated the role of serum starvation in regulating HIV-1 latency. The impact of serum starvation on HIV-1 latency was assessed in latently infected monocytes U1 and T-cells J1.1. Serum starvation breaks HIV-1 latency in U1 cells. Under similar conditions, J1.1 cells failed to show reactivation of virus. We investigated the involvement of cell death pathway and autophagy during the serum starvation in viral reactivation. Inhibition of these pathways did not affect viral reactivation. Furthermore, other crucial factors like NF-κB, SP1 and AKT did not play any role in regulating viral latency. Here, we report that serum deprivation up-regulates ERK/JNK pathway. This leads to phosphorylation of c-Jun which plays an important role in viral reactivation. Treatment of cells with U0126, an ERK kinase inhibitor, potently inhibited viral replication. In summary, we show that serum starvation leads to reactivation of HIV-1 in latently infected monocytes through the ERK/JNK pathway.


Asunto(s)
Infecciones por VIH/enzimología , VIH-1/fisiología , Sistema de Señalización de MAP Quinasas , Monocitos , Activación Viral/fisiología , Latencia del Virus/fisiología , Autofagia , Línea Celular , Infecciones por VIH/patología , Humanos , Monocitos/enzimología , Monocitos/patología , Monocitos/virología , Activación Viral/efectos de los fármacos , Latencia del Virus/efectos de los fármacos
12.
Mol Immunol ; 97: 82-93, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29602073

RESUMEN

BACKGROUND: The combinatorial effects of Plasmodium infection, perturbation of inflammatory responses and the dichotomic role of TNF promoter polymorphism has potential clinical and physiological relevance during pregnancy. OBJECTIVE AND METHODS: This coordinated orchestration instigated us to investigate the circulating level of inflammatory cytokines (IL-1ß, TNF-α and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-α -308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. RESULTS: We observed significantly elevated concentrations of IL-1ß were observed, followed by IL-6 and TNF-α in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1ß, followed by TNF-α and IL-6 were detected in the non-infected pregnancy group. The differential dynamics of inflammatory cytokine concentration during each trimester of pregnancy with and without P. vivax infection were detected. For the first time, a high level of IL-6 was observed in the first trimester of MIP and high IL-1ß in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1ß in the MIP group compared to a sustained high level of IL-1ß in the healthy pregnancy group. In the third trimester, high IL-1ß was sustained in the MIP group and healthy pregnancies acquired a high TNF-α level. The genotypic distribution for the TNF-α promoter -308 G/A position was observed to be nonsignificant and mildly associated during MIP (OR = 1.4) and in WWM (OR = 1.2). Moreover, based on genotypic distribution, we observed a well-correlated and significantly elevated TNF-α concentration in the mutant homozygote genotype (AA; p = 0.001) followed by heterozygotes (GA; p = 0.0001) and ancestral genotypes (GG; p = 0.0001) in both MIP and WWM subjects. CONCLUSION: The observation of elevated IL-1ß and IL-6 in MIP and TNF-α in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly, the TNF-α concentration and its polymorphic variability in the promoter region may indicate genetic susceptibility and mildly influence the risk for P. vivax infection during pregnancy and in women with malaria.


Asunto(s)
Interleucina-1beta/sangre , Interleucina-6/sangre , Malaria Vivax/sangre , Malaria Vivax/genética , Plasmodium vivax , Complicaciones Parasitarias del Embarazo , Factor de Necrosis Tumoral alfa/genética , Adulto , Biomarcadores/sangre , Estudios Transversales , Enfermedades Endémicas , Femenino , Predisposición Genética a la Enfermedad , Humanos , India/epidemiología , Interleucina-1beta/fisiología , Interleucina-6/fisiología , Malaria Vivax/epidemiología , Malaria Vivax/inmunología , Persona de Mediana Edad , Plasmodium vivax/inmunología , Polimorfismo Genético , Embarazo , Complicaciones Parasitarias del Embarazo/sangre , Complicaciones Parasitarias del Embarazo/epidemiología , Complicaciones Parasitarias del Embarazo/genética , Complicaciones Parasitarias del Embarazo/inmunología , Regiones Promotoras Genéticas , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/fisiología , Adulto Joven
13.
Ann Intern Med ; 168(2): 100-109, 2018 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-29204651

RESUMEN

Background: The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. Objective: To study the diagnostic utility of WES in a selected referral population of adults with CKD. Design: Observational cohort. Setting: A major academic medical center. Patients: 92 adults with CKD of unknown cause or familial nephropathy or hypertension. Measurements: The diagnostic yield of WES and its potential effect on clinical management. Results: Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. Limitation: The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Conclusion: Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. Primary Funding Source: New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of Health.


Asunto(s)
Exoma/genética , Insuficiencia Renal Crónica/genética , Análisis de Secuencia de ADN/métodos , Adulto , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Ciudad de Nueva York
15.
Pol J Radiol ; 82: 410-417, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28819463

RESUMEN

BACKGROUND: The study aimed to evaluate of the role of high-resolution ultrasound and magnetic resonance imaging in patients with shoulder pain. MATERIAL/METHODS: This prospective study included 50 patients referred for ultrasound and MRI because of shoulder pain. All patients were examined clinically, followed by radiography of the affected shoulder. High-resolution ultrasound examination of the involved shoulder was performed together with an examination of the contralateral normal shoulder, followed by MRI of the symptomatic shoulder in all 50 patients. RESULTS: In the present study, the majority of patients were in age group 56-65 years, 56% were males and 44% were females (of a total of 50 patients). A total of 40 patients were diagnosed as having rotator cuff tears on ultrasound (USG) and MRI. USG showed complete-thickness tears in 25 patients and partial-thickness tears in 15 patients. MRI detected 28 complete- and 12 partial-thickness tears of the rotator cuff. In the diagnosis of rotator cuff tears, the strength of agreement between ultrasound and magnetic resonance imaging was good (kappa coefficient=0.79). CONCLUSIONS: Ultrasonography of the shoulder shows promising results in the diagnosis of rotator cuff tears and in differentiating partial from complete tears. A wide availability, cost effectiveness and better tolerability of ultrasonography make it a modality of first choice for evaluating rotator cuff tears.

16.
Biochem J ; 474(14): 2449-2464, 2017 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-28468838

RESUMEN

Murine double minute 2 (Mdm2) is known to enhance the transactivation potential of human immunodeficiency virus (HIV-1) Tat protein by causing its ubiquitination. However, the regulation of Mdm2 during HIV-1 infection and its implications for viral replication have not been well studied. Here, we show that the Mdm2 protein level increases during HIV-1 infection and this effect is mediated by HIV-1 Tat protein. Tat appears to stabilise Mdm2 at the post-translational level by inducing its phosphorylation at serine-166 position through AKT. Although p53 is one of the key players for Mdm2 induction, Tat-mediated stabilisation of Mdm2 appears to be independent of p53. Moreover, the non-phosphorylatable mutant of Mdm2 (S166A) fails to interact with Tat and shows decreased half-life in the presence of Tat compared with wild-type Mdm2. Furthermore, the non-phosphorylatable mutant of Mdm2 (S166A) is unable to support HIV-1 replication. Thus, HIV-1 Tat appears to stabilise Mdm2, which in turn enhances Tat-mediated viral replication. This study highlights the importance of post-translational modifications of host cellular factors in HIV-1 replication and pathogenesis.


Asunto(s)
VIH-1/fisiología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Mutación , Fosforilación , Proteínas Proto-Oncogénicas c-mdm2/genética , ARN Interferente Pequeño/genética , Proteína p53 Supresora de Tumor/metabolismo , Replicación Viral
17.
Indian J Anaesth ; 60(6): 403-8, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27330202

RESUMEN

BACKGROUND AND AIMS: Total knee replacement (TKR) patients experience considerable post-operative pain. We evaluated whether addition of perineural dexmedetomidine to ropivacaine 0.2% in the femoral nerve block would enhance post-operative analgesia in patients undergoing unilateral TKR under spinal anaesthesia. METHODS: Fifty patients were allocated randomly to two groups of 25 each. Group D received ropivacaine (0.2%) with dexmedetomidine (1.5 µg/kg), and Group C received ropivacaine (0.2%) with normal saline. Pain scores, time to the first request for analgesia and total consumption of ropivacaine in 48 h, along with haemodynamic parameters and sedation scores, were recorded. Quantitative data were compared using t-test, categorical data using Chi-square or Fisher's exact test and time variables using ANOVA. RESULTS: The mean pain scores were significantly low till 2 h post-operatively in Group D. Time to the first demand for analgesia after initial loading dose was statistically prolonged in Group D, with mean duration of 346.8 ± 240 min, compared to 150 ± 115.2 min in Group C (P = 0.001). Total local anaesthetic consumption was also decreased over 24 and 48 h in Group D (P = 0.001). Haemodynamically, there was no significant variation in heart rate from their baseline mean values in either group (P > 0.05). However, the drop in systolic and mean blood pressure post-surgery was significant till 4 (P = 0.002) and 8 h (P = 0.02), respectively, in Group D. Group D patients were also significantly more sedated till 4 h post-operatively (P < 0.005). CONCLUSION: Adding dexmedetomidine to ropivacaine 0.2% in the femoral nerve block in patients undergoing unilateral TKR improves the quality and prolongs the duration of post-operative analgesia.

18.
J Environ Manage ; 166: 387-406, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26546885

RESUMEN

Many researchers have used nanoparticles as adsorbents to remove water pollutants including arsenic after modifying the properties of nanoparticles by improving reactivity, biocompatibility, stability, charge density, multi-functionalities, and dispersibility. For arsenic removal, nano adsorbents emerged as the potential alternatives to existing conventional technologies. The present study critically reviewed the past and current available information on the potential of nano adsorbents for arsenic removal from contaminated water and the challenges involved in that. The study discussed the separation and regeneration techniques of nano adsorbents and the performance thereof. The study evaluated the adsorption efficiency of the various nanoparticles based on size of nanoparticles, types of nano adsorbents, method of synthesis, separation and regeneration of the nano adsorbents. The study found that more studies are required on suitable holding materials for the nano adsorbents to improve the permeability and to make the technology applicable at the field condition. The study will help the readers to choose suitable nanomaterials and to take up further research required for arsenic removal using nano adsorbents.


Asunto(s)
Arsénico/análisis , Nanopartículas/química , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Adsorción , Arsénico/química , Agua/química , Contaminantes Químicos del Agua/química
19.
Nat Commun ; 6: 7244, 2015 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-26059226

RESUMEN

HIV-1 gene expression and replication largely depend on the regulatory proteins Tat and Rev, but it is unclear how the intracellular levels of these viral proteins are regulated after infection. Here we report that HIV-1 Rev causes specific degradation of cytoplasmic Tat, which results in inhibition of HIV-1 replication. The nuclear export signal (NES) region of Rev is crucial for this activity but is not involved in direct interactions with Tat. Rev reduces the levels of ubiquitinated forms of Tat, which have previously been reported to be important for its transcriptional properties. Tat is stabilized in the presence of NAD(P)H: quinine oxidoreductase 1 (NQO1), and potent degradation of Tat is induced by dicoumarol, an NQO1 inhibitor. Furthermore, Rev causes specific reduction in the levels of endogenous NQO1. Thus, we propose that Rev is able to induce degradation of Tat indirectly by downregulating NQO1 levels. Our findings have implications in HIV-1 gene expression and latency.


Asunto(s)
Productos del Gen rev/metabolismo , Productos del Gen tat/metabolismo , VIH-1/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Replicación Viral , VIH-1/fisiología , Señales de Exportación Nuclear , Proteolisis
20.
Biomed Res Int ; 2015: 740512, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26783526

RESUMEN

The escalating burden, pathogenesis, and clinical sequel of malaria during pregnancy have combinatorial adverse impact on both mother and foetus that further perplexed the situation of diagnosis, treatment, and prevention. This prompted us to evaluate the status of population at risk of MIP in Hazaribag, Jharkhand, India. Cross-sectional study was conducted over a year at Sadar Hospital, Hazaribag. Malaria was screened using blood smear and/or RDT. Anaemia was defined as haemoglobin concentration. Pretested questionnaires were used to gather sociodemographic, clinical, and obstetrical data. The prevalence of MIP was 5.4% and 4.3% at ANC and DU, and 13.2% malaria was in women without pregnancy. Interestingly, majority were asymptomatically infected with P. vivax (over 85%) at ANC and DU. Peripheral parasitemia was significantly associated with fever within past week, rural origin of subjects, and first/second pregnancies in multivariate analysis, with the highest risk factor associated with fever followed by rural residence. Strikingly in cohort, anaemia was prevalent in 86% at ANC as compared to 72% at DU, whereas severe anaemia was 13.6% and 7.8% at ANC and DU. Even more anaemia prevalence was observed in MIP group (88% and 89% at ANC and DU), whereas severe anaemia was 23% and 21%, respectively. In view of observed impact of anaemia, parasitemia and asymptomatic infection of P. vivax during pregnancy and delivery suggest prompt diagnosis regardless of symptoms and comprehensive drug regime should be offered to pregnant women in association with existing measures in clinical spectrum of MIP, delivery, and its outcome.


Asunto(s)
Anemia/epidemiología , Fiebre/epidemiología , Malaria Falciparum/epidemiología , Parasitemia/epidemiología , Adulto , Anemia/complicaciones , Anemia/parasitología , Femenino , Fiebre/parasitología , Humanos , India , Malaria Falciparum/complicaciones , Malaria Falciparum/parasitología , Parasitemia/parasitología , Embarazo , Complicaciones Parasitarias del Embarazo , Factores de Riesgo
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