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1.
Environ Monit Assess ; 196(3): 320, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418623

RESUMO

The discharge of industrial effluents has a significant impact on the Water Quality Index (WQI) of the water bodies and is a major source of contamination of groundwater. The present study investigated the physicochemical characteristics and scrutinized the pollution potential of the tannery, textile, and electroplating effluents uploading into the Kala Sanghian drain, located in Jalandhar, Punjab, India. In this study, 12 samples were collected from the four sites (leather complex drain (LD), leather complex outlet (LO), focal point drain (FD), and Bulandpur drain (BD)) of Kala Sanghian drain in the dry season. The result showed that the drain under consideration is very much contaminated and the water is not suitable for irrigation and agricultural purposes. Rather it has a bad impact on the health of local people, the physiology of aquatic organisms, and the soil quality of agricultural land nearby. The present study confirmed the water quality index was more than 100, indicating a highly contaminated drain and water is unfit for any use. The correlation analysis shows that there exists a positive correlation between TDS and temperature (r = 0.994), DO and pH (r = 0.808), BOD and temperature (r = 0.987), BOD and TDS (r = 0.978), EC and temperature (r = 0.963), EC and TDS (r = 0.954), and EC and BOD (r = 0.956). The principal component analysis (PCA) confirms that PC1 alone has more than 89% of the variance with high positive loading for TDS, temperature, EC, and BOD. The hierarchical cluster analysis (HCA) reflected two clusters where cluster 1 consists of pH, DO, temperature, and BOD of water while cluster 2 consists of TDS and EC of water. The PCA and HCA study of the data set confirms the high degree contribution of anthropogenic activities through the application of chemicals in agriculture, disposal of municipal waste, and industrial effluents in the deterioration of water quality. The results of the study will help to enhance the sustainable action plan for the management of industrial effluents in the studied area.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Indústrias , Análise por Conglomerados , Agricultura , Solo , Qualidade da Água , Índia , Poluentes Químicos da Água/análise
2.
J Exp Bot ; 73(11): 3584-3596, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35290448

RESUMO

Sorghum is a feed/industrial crop in developed countries and a staple food elsewhere in the world. This study evaluated the sorghum mini core collection for days to 50% flowering (DF), biomass, plant height (PH), soluble solid content (SSC), and juice weight (JW), and the sorghum reference set for DF and PH, in 7-12 testing environments. We also performed genome-wide association mapping with 6 094 317 and 265 500 single nucleotide polymorphism markers in the mini core collection and the reference set, respectively. In the mini core panel we identified three quantitative trait loci for DF, two for JW, one for PH, and one for biomass. In the reference set panel we identified another quantitative trait locus for PH on chromosome 6 that was also associated with biomass, DF, JW, and SSC in the mini core panel. Transgenic studies of three genes selected from the locus revealed that Sobic.006G061100 (SbSNF4-2) increased biomass, SSC, JW, and PH when overexpressed in both sorghum and sugarcane, and delayed flowering in transgenic sorghum. SbSNF4-2 encodes a γ subunit of the evolutionarily conserved AMPK/SNF1/SnRK1 heterotrimeric complexes. SbSNF4-2 and its orthologs will be valuable in genetic enhancement of biomass and sugar yield in plants.


Assuntos
Saccharum , Sorghum , Biomassa , Carboidratos , Grão Comestível/genética , Estudo de Associação Genômica Ampla , Fenótipo , Saccharum/genética , Sorghum/genética , Açúcares
3.
Sensors (Basel) ; 22(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458999

RESUMO

Advances in 5G and the Internet of Things (IoT) have to cater to the diverse and varying needs of different stakeholders, devices, sensors, applications, networks, and access technologies that come together for a dedicated IoT network for a synergistic purpose. Therefore, there is a need for a solution that can assimilate the various requirements and policies to dynamically and intelligently orchestrate them in the dedicated IoT network. Thus we identify and describe a representative industry-relevant use case for such a smart and adaptive environment through interviews with experts from a leading telecommunication vendor. We further propose and evaluate candidate architectures to achieve dynamic and intelligent orchestration in such a smart environment using a systematic approach for architecture design and by engaging six senior domain and IoT experts. The candidate architecture with an adaptive and intelligent element ("Smart AAA agent") was found superior for modifiability, scalability, and performance in the assessments. This architecture also explores the enhanced role of authentication, authorization, and accounting (AAA) and makes the base for complete orchestration. The results indicate that the proposed architecture can meet the requirements for a dedicated IoT network, which may be used in further research or as a reference for industry solutions.


Assuntos
Internet das Coisas , Indústrias , Tecnologia
4.
Adv Exp Med Biol ; 1302: 99-111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34286444

RESUMO

Multiple checkpoint mechanisms are overridden by cancer cells in order to develop into a tumor. Neoplastic cells, while constantly changing during the course of cancer progression, also craft their surroundings to meet their growing needs. This crafting involves changing cell surface receptors, affecting response to extracellular signals and secretion of signals that affect the nearby cells and extracellular matrix architecture. This chapter briefly comprehends the non-cancer cells facilitating the cancer growth and elaborates on the notable role of the CCR9-CCL25 chemokine axis in shaping the tumor microenvironment (TME), directly and via immune cells. Association of increased CCR9 and CCL25 levels in various tumors has demonstrated the significance of this axis as a tool commonly used by cancer to flourish. It is involved in attracting immune cells in the tumor and determining their fate via various direct and indirect mechanisms and, leaning the TME toward immunosuppressive state. Besides, elevated CCR9-CCL25 signaling allows survival and rapid proliferation of cancer cells in an otherwise repressive environment. It modulates the intra- and extracellular protein matrix to instigate tumor dissemination and creates a supportive metastatic niche at the secondary sites. Lastly, this chapter abridges the latest research efforts and challenges in using the CCR9-CCL25 axis as a cancer-specific target.


Assuntos
Receptores CCR , Microambiente Tumoral , Transdução de Sinais
5.
Cancer Cell Int ; 19: 98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011292

RESUMO

BACKGROUND: Currently offered therapeutics to treat colon cancer (CoCa) are toxic when given at maximum tolerated dose to achieve optimal clinical response. Hence, less toxic therapeutic intervention is needed to treat CoCa. In this study, we investigated the effect of a natural agent, Emodin, on CoCa. METHODS: Cell viability (MTT) assay was used to determine the effect of Emodin on human CoCa and colon epithelial cells. Flow cytometric analysis was used to determine Emodin induced cell death. Antibody microarray and western blot analyses were used to determine Emodin induced molecular changes involved in cell death. Change in mitochondrial membrane potential in response to Emodin was determined by flow cytometric analysis. Expression and localization of Bcl-2 family proteins were assessed by western blot analysis. RESULTS: Emodin decreased viability of CoCa cells and induced apoptosis in a time and dose-dependent manner compared to vehicle-treated control without significantly impacting normal colon epithelial cells. Emodin activated caspases, modulated Bcl-2 family of proteins and reduced mitochondrial membrane potential to induce CoCa cell death. Further, changes in Bcl-2 family protein expression and localization correlated with loss in mitochondrial membrane potential. Signaling (MAPK/JNK, PI3K/AKT, NF-κß and STAT) pathways associated with cell growth, differentiation, and Bcl-2 family expression or function were negatively regulated by Emodin. CONCLUSIONS: Ability of Emodin to impact molecular pathways involved in cell survival and apoptosis highlight the potential of this agent as a new and less toxic alternative for CoCa treatment.

6.
Org Biomol Chem ; 17(38): 8711-8715, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31549123

RESUMO

A chemoenzymatic reduction of citreorosein by the NADPH-dependent polyhydroxyanthracene reductase from Cochliobolus lunatus or MdpC from Aspergillus nidulans in the presence of Na2S2O4 gave access to putative biosynthetic intermediates, (R)-3,8,9,10-tetrahydroxy-6-(hydroxymethyl)-3,4-dihydroanthracene-1(2H)-one and its oxidized form, (R)-3,4-dihydrocitreorosein. Herein, we discuss the implications of these results towards the (bio)synthesis of aloe-emodin and (+)-rugulosin C in fungi.


Assuntos
Antraquinonas/metabolismo , Proteínas Fúngicas/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Antraquinonas/química , Ascomicetos/enzimologia , Proteínas Fúngicas/química , Estrutura Molecular , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química
7.
Chembiochem ; 19(15): 1657-1663, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-29790650

RESUMO

Superoxide (O2.- ) generation in biological systems is achieved through some of the most complex enzymatic systems. Of these, only xanthine/xanthine oxidase has been used for in vitro biochemical studies. However, it suffers from limitations such as a lack of suitable heterologous expression system for xanthine oxidase and the irreversible consumption and low solubility of xanthine under physiological conditions. Herein, we report a redox-based, enzyme-catalyzed system, in which autoxidation of hydroquinone to quinone via semiquinone results in superoxide generation. Quinone is reduced back to hydroquinone by using the NfsB (oxygen-insensitive nitroreductase) enzyme of Escherichia coli strain K-12 and nicotinamide adenine dinucleotide phosphate hydride (NADPH; which is regenerated by using the glucose/glucose dehydrogenase system). This new system relies on quinones that can be recycled and have superior water solubility, as well as enzymes that are heterologously expressed. By using a variety of quinones and reaction conditions, along with a comparison of real-time fluorescence, menadione has been identified as the optimal substrate for superoxide generation. The new redox-based system presents a viable alternative for studying the biochemistry of superoxide under different physiological and pathological conditions.


Assuntos
Benzoquinonas/metabolismo , Escherichia coli K12/metabolismo , Proteínas de Escherichia coli/metabolismo , Hidroquinonas/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Nitrorredutases/metabolismo , Superóxidos/metabolismo , Cinética , Oxirredução , Oxigênio/metabolismo
8.
Chemistry ; 24(6): 1283-1286, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29266494

RESUMO

Modified bisanthraquinones are complex dimeric natural products containing a cage-like structural motif. For their biosynthesis, monomeric dihydroanthraquinones have been proposed as key intermediates despite not being isolated from natural sources or synthesized as of yet. Here, isolation and characterization of dihydroemodin, as well as dihydrolunatin, synthesized by a biomimetic and chemoenzymatic approach using NADPH-dependent polyhydroxyanthracence reductase (PHAR) from Cochliobolus lunatus followed by Pb(OAc)4 oxidation is reported. Subsequent dimerization through a hetero-Diels-Alder reaction of the dihydroemodin and dihydrolunatin resulted in (-)-flavoskyrin (68 %) and (-)-lunaskyrin (62 %), respectively. Pyridine treatment of (-)-flavoskyrin and (-)-lunaskyrin gave (-)-rugulosin and (-)-2,2'-epi-cytoskyrin A in 64 % and 60 % yield, respectively, through a cascade that involves two dimeric intermediates. Implications of the described synthesis for the biosynthesis of bisanthraquinones by a combination of enzymatic and spontaneous steps are discussed.


Assuntos
Antraquinonas/síntese química , Produtos Biológicos/química , Antraquinonas/química , Ascomicetos/enzimologia , Catálise , Reação de Cicloadição , Dimerização , Compostos Organometálicos/química , Oxirredução , Oxirredutases/química , Piridinas/química
9.
World J Surg Oncol ; 16(1): 108, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29898731

RESUMO

BACKGROUND: Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death. METHODS: Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin. RESULTS: PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death. CONCLUSIONS: Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Quercetina/farmacologia , Quercetina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Prognóstico
10.
J Environ Manage ; 222: 293-303, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29860123

RESUMO

In New Zealand, there is substantial potential for microbial contaminants from agricultural fecal sources to be transported into waterways. The flow and transport pathways for fecal contaminants vary at a range of scales and is dependent on chemical, physical and biological attributes of pathways, soils, microorganisms and landscape characteristics. Understanding contaminant transport pathways from catchment to stream can aid water management strategies. It is not practical, however to conduct direct field measurement for all catchments on the fate and transport of fecal pathogens due to constraints on time, personnel, and material resources. To overcome this problem, fecal source tracking can be utilised to link catchment characteristics to fecal signatures identifying critical sources. In this article, we have reviewed approaches to identifying critical sources and pathways for fecal microorganisms from agricultural sources, and make recommendations for the appropriate use of these fecal source tracking (FST) tools.


Assuntos
Agricultura , Fezes , Microbiologia da Água , Monitoramento Ambiental , Nova Zelândia , Rios , Qualidade da Água
11.
Chembiochem ; 18(1): 77-80, 2017 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-27906500

RESUMO

17ß-Hydroxysteroid dehydrogenase (17ß-HSDcl) from the filamentous fungus Curvularia lunata (teleomorph Cochliobolus lunatus) catalyzes NADP(H)-dependent oxidoreductions of androgens and estrogens. Despite detailed biochemical and structural characterization of 17ß-HSDcl, its physiological function remains unknown. On the basis of amino acid sequence alignment, phylogenetic studies, and the recent identification of the physiological substrates of the homologous MdpC from Aspergillus nidulans and AflM from Aspergillus parasiticus, we propose an anthrahydroquinone as the physiological substrate of 17ß-HSDcl. This is also supported by our analysis of a secondary metabolite biosynthetic gene cluster in C. lunata m118, containing 17ß-HSDcl and ten other genes, including a polyketide synthase probably involved in emodin formation. Chemoenzymatic reduction of emodin by 17ß-HSDcl in the presence of sodium dithionite verified this hypothesis. On the basis of these results, the involvement of a 17ß-HSDcl in the biosynthesis of other anthrahydroquinone-derived natural products is proposed; hence, 17ß-HSDcl should be more appropriately referred to as a polyhydroxyanthracene reductase (PHAR).


Assuntos
17-Hidroxiesteroide Desidrogenases/metabolismo , Antraquinonas/metabolismo , Ascomicetos/enzimologia , 17-Hidroxiesteroide Desidrogenases/classificação , 17-Hidroxiesteroide Desidrogenases/genética , Antraquinonas/química , Ascomicetos/genética , Biocatálise , Emodina/química , Emodina/metabolismo , Família Multigênica , Oxirredução , Filogenia
12.
Br J Cancer ; 114(12): 1343-51, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27149649

RESUMO

BACKGROUND: Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway. METHODS: Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20. RESULTS: CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, ß-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential. CONCLUSIONS: Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.


Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Receptores CCR6/biossíntese , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Quimiocina CCL20/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Transdução de Sinais
13.
Immunology ; 141(4): 514-30, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24138116

RESUMO

Pneumococcal surface adhesin A (PsaA) is a multifunctional lipoprotein known to bind nasopharyngeal epithelial cells, and is significantly involved in bacterial adherence and virulence. Identification of PsaA peptides that optimally bind human leucocyte antigen (HLA) and elicit a potent immune response would be of great importance to vaccine development. However, this is hindered by the multitude of HLA polymorphisms in humans. To identify the conserved immunodominant epitopes, we used an experimental dataset of 28 PsaA synthetic peptides and in silico methods to predict specific peptide-binding to HLA and murine MHC class II molecules. We also characterized spleen and cervical lymph node (CLN) -derived T helper (Th) lymphocyte cytokine responses to these peptides after Streptococcus pneumoniae strain EF3030 challenge in mice. Individual, yet overlapping, peptides 15 amino acids in length revealed residues of PsaA that consistently caused the highest interferon-γ, interleukin-2 (IL-2), IL-5 and IL-17 responses and proliferation as well as moderate IL-10 and IL-4 responses by ex vivo re-stimulated splenic and CLN CD4⁺ T cells isolated from S. pneumoniae strain EF3030-challenged F1 (B6 × BALB/c) mice. In silico analysis revealed that peptides from PsaA may interact with a broad range of HLA-DP, -DQ and -DR alleles, due in part to regions lacking ß-turns and asparagine endopeptidase sites. These data suggest that Th cell peptides (7, 19, 20, 22, 23 and 24) screened for secondary structures and MHC class II peptide-binding affinities can elicit T helper cytokine and proliferative responses to PsaA peptides.


Assuntos
Proteínas de Bactérias/imunologia , Mapeamento de Epitopos , Epitopos de Linfócito T , Epitopos Imunodominantes , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proliferação de Células , Técnicas de Cocultura , Células Alimentadoras , Feminino , Antígenos HLA/imunologia , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Interferon gama/metabolismo , Interleucinas/metabolismo , Linfonodos/imunologia , Linfonodos/microbiologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Dados de Sequência Molecular , Infecções Pneumocócicas/metabolismo , Infecções Pneumocócicas/microbiologia , Ligação Proteica , Estrutura Secundária de Proteína , Baço/imunologia , Baço/microbiologia , Streptococcus pneumoniae/metabolismo , Linfócitos T Auxiliares-Indutores/microbiologia
14.
J Biotechnol ; 382: 51-69, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38242502

RESUMO

Volatile organic compounds (VOCs) are the organic compounds having a minimum vapor pressure of 0.13 kPa at standard temperature and pressure (293 K, 101 kPa). Being used as a solvent for organic and inorganic compounds, they have a wide range of applications. Most of the VOCs are non-biodegradable and very easily become component of the environment and deplete its purity. It also deteriorates the water quality index of the water bodies, impairs the physiology of living beings, enters the food chain by bio-magnification and degrades, decomposes and manipulates the physiology of living organisms. To unveil the adverse impacts of volatile organic compounds (VOCs) and their rapid eruption and interference in the living world, a review has been designed. This review presents an insight into the currently available VOCs, their sources, applications, sampling methods, analytic procedures, imposition on the health of aquatic and terrestrial communities and their contamination of the environment. Elaboration has been done on representation of toxicological effects of VOCs on vertebrates, invertebrates, and birds. Subsequently, the role of environmental agencies in the protection of environment has also been illustrated.


Assuntos
Monitoramento Ambiental , Compostos Orgânicos Voláteis , Animais , Monitoramento Ambiental/métodos , Compostos Orgânicos Voláteis/toxicidade
15.
Cancers (Basel) ; 16(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38927911

RESUMO

Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals' cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies.

16.
Cancers (Basel) ; 16(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38339362

RESUMO

Lung cancer remains a leading cause of death in the United States and globally, despite progress in treatment and screening efforts. While mortality rates have decreased in recent years, long-term survival of patients with lung cancer continues to be a challenge. Notably, African American (AA) men experience significant disparities in lung cancer compared to European Americans (EA) in terms of incidence, treatment, and survival. Previous studies have explored factors such as smoking patterns and complex social determinants, including socioeconomic status, personal beliefs, and systemic racism, indicating their role in these disparities. In addition to social factors, emerging evidence points to variations in tumor biology, immunity, and comorbid conditions contributing to racial disparities in this disease. This review emphasizes differences in smoking patterns, screening, and early detection and the intricate interplay of social, biological, and environmental conditions that make African Americans more susceptible to developing lung cancer and experiencing poorer outcomes.

17.
Mol Cancer ; 12: 64, 2013 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-23773523

RESUMO

BACKGROUND: Prostate cancer (PCa) cell lines and tissues differentially express CXCR5, which positively correlate with PCa progression, and mediate PCa cell migration and invasion following interaction with CXCL13. However, the differential expression of G protein α, ß, and γ subunits by PCa cell lines and the precise combination of these proteins with CXCR5 has not been elucidated. METHODS: We examined differences in G protein expression of normal prostate (RWPE-1) and PCa cell lines (LNCaP, C4-2B, and PC3) by western blot analysis. Further, we immunoprecipitated CXCR5 with different G protein subunits, and CXCR4, following CXCL13 stimulation. To investigate constitutive coupling of CXCR5 with CXCR4 and PAR-1 we performed invasion assay in PCa cells transfected with Gαq/i2 or Gα13 siRNA, following CXCL13 treatment. We also investigated Rac and RhoA activity by G-LISA activation assay in PCa cells following CXCL13/thrombin stimulation. RESULT: Of the 22 G proteins studied, Gαi1-3, Gß1-4, Gγ5, Gγ7, and Gγ10 were expressed by both normal and PCa cell lines. Gαs was moderately expressed in C4-2B and PC3 cell lines, Gαq/11 was only present in RWPE-1 and LNCaP cell lines, while Gα12 and Gα13 were expressed in C4-2B and PC3 cell lines. Gγ9 was expressed only in PCa cell lines. Gα16, Gß5, Gγ1-4, and Gγ13 were not detected in any of the cell lines studied. Surprisingly, CXCR4 co-immunoprecipitated with CXCR5 in PCa cell lines irrespective of CXCL13 treatment. We also identified specific G protein isoforms coupled to CXCR5 in its resting and active states. Gαq/11/Gß3/Gγ9 in LNCaP and Gαi2/Gß3/Gγ9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. Interestingly, Gα13 co-immunoprecipitated with CXCR5 in CXCL13-treated, but not in untreated PCa cell lines. Inhibition of Gαq/i2 significantly decreased the ability of cells to invade, whereas silencing Gα13 did not affect CXCL13-dependent cell invasion. Finally, CXCL13 treatment significantly increased Rac activity in Gαq/i2 dependent manner, but not RhoA activity, in PCa cell lines. CONCLUSIONS: These findings offer insight into molecular mechanisms of PCa progression and can help to design some therapeutic strategies involving CXCR5 and/or CXCL13 blockade and specific G protein inhibition to abrogate PCa metastasis.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Neoplasias da Próstata/metabolismo , Subunidades Proteicas/metabolismo , Receptores CXCR5/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL13/farmacologia , Humanos , Masculino , Modelos Biológicos , Neoplasias da Próstata/patologia , Ligação Proteica/efeitos dos fármacos , Isoformas de Proteínas/metabolismo , Receptor PAR-1/metabolismo , Receptores CXCR4/metabolismo , Reprodutibilidade dos Testes , Trombina/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
18.
Lepr Rev ; 84(2): 136-40, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24171239

RESUMO

Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis.


Assuntos
Abscesso/microbiologia , Hanseníase Tuberculoide/complicações , Hanseníase/complicações , Neurite (Inflamação)/microbiologia , Abscesso/patologia , Adolescente , Mãos/inervação , Mãos/patologia , Humanos , Hanseníase/patologia , Hanseníase Tuberculoide/patologia , Masculino , Neurite (Inflamação)/patologia
19.
Indian J Dermatol Venereol Leprol ; 89(5): 647-655, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37067143

RESUMO

Background Androgenetic alopecia is a common, chronic, non-scarring alopecia. It is characterised by stepwise miniaturisation of the hair follicles, due to alteration in the hair cycle dynamics, leading to the transformation of terminal hair follicles into a vellus ones. Oral finasteride and topical minoxidil are the only approved drugs for treating this condition. Due to a limited number of effective therapies for androgenetic alopecia, platelet-rich plasma may be an effective alternative treatment. Aims To study the effect of activator in platelet-rich plasma and baseline platelet count in platelet-rich plasma on the treatment of androgenetic alopecia. Methods A randomised, double-blind split-head comparative study. The sample size was calculated and randomisation was done. Patients with androgenetic alopecia were allocated into two groups; in the first group, autologous activated platelet-rich plasma was injected in the right half of the affected scalp and autologous non-activated platelet-rich plasma was injected in the left half of the affected scalp and vice versa in the second group. Patients were also categorised on the basis of platelet counts in their platelet-rich plasma in three groups; group A (6-8 lakh/mm3), group B (8.1-10 lakh/mm3) and group C (>10 lakh/mm3). Interventions were done monthly for three months and followed up for the next three months. Effects of interventions were assessed by hair density, hair thickness, patient self-assessment and clinical photography. Results A total of 80 patients were included in the study. Activated platelet-rich plasma produced significant improvement of hair density after four months and hair thickness at 6 months. An increase in platelet count led to a significant increase in hair density and hair thickness after three and four months respectively and a highly significant increase in both parameters at the end of the study. Limitations Long-term follow-up of cases was not done and no measurement of vellus hair count was done. Conclusion There is a significant effect of activator and platelet count of the platelet-rich plasma on hair density as well as hair thickness.


Assuntos
Alopecia , Plasma Rico em Plaquetas , Humanos , Contagem de Plaquetas , Método Duplo-Cego , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Cabelo , Minoxidil , Resultado do Tratamento
20.
Transl Oncol ; 16: 101330, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34990909

RESUMO

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite increased screening options and state-of-art treatments offered in clinics, racial differences remain in CRC. African Americans (AAs) are disproportionately affected by the disease; the incidence and mortality are higher in AAs than Caucasian Americans (CAs). At the time of diagnosis, AAs more often present with advanced stages and aggressive CRCs, primarily accounting for the racial differences in therapeutic outcomes and mortality. The early incidence of CRC in AAs could be attributed to race-specific gene polymorphisms and lifestyle choices associated with socioeconomic status (SES). Altered melatonin-serotonin signaling, besides the established CRC risk factors (age, diet, obesity, alcoholism, and tobacco use), steered by SES, glucocorticoid, and Vitamin D status in AAs could also account for the early incidence in this racial group. This review focuses on how the lifestyle factors, diet, allelic variants, and altered expression of specific genes could lead to atypical serotonin and melatonin signaling by modulating the synthesis, secretion, and signaling of these pineal hormones in AAs and predisposing them to develop more aggressive CRC earlier than CAs. Crosstalk between gut microbiota and pineal hormones and its impact on CRC pathobiology is addressed from a race-specific perspective. Lastly, the status of melatonin-focused CRC treatments, the need to better understand the perturbed melatonin signaling, and the potential of pineal hormone-directed therapeutic interventions to reduce CRC-associated disparity are discussed.

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