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1.
Org Lett ; 26(15): 2993-2998, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38592728

RESUMO

Functionalization of C(sp3)-H bonds represents the most straightforward and atom-economical transformation in organic synthesis. An innovative approach integrating photocatalytic hydrogen atom transfer (HAT) and transition metal catalysis has made significant progress in the coupling of α-heterosubstituted C-H bonds with alkyl halides. However, unactivated alkanes were ineffective as a result of the preponderance of byproduct formation. Herein, we demonstrate direct HAT and nickel catalysis in the coupling of cycloalkanes and benzyl bromides/primary alkyl iodides. Additionally, tetrabutylammonium decatungstate (TBADT) was recovered and recycled.

2.
Cureus ; 16(1): e52324, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38361692

RESUMO

BACKGROUND:  Coronavirus disease 2019 (COVID-19) is a potentially lethal respiratory illness caused by a newly identified coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the novelty of the virus, high caseloads, and increasing turnaround time for reverse transcriptase-polymerase chain reaction (RT-PCR) results, accurate information about the clinical course and prognosis of individual patients was largely unknown. This has forced physicians all over the world to brainstorm attempts to come up with reliable indicators like chest high-resolution computed tomography (HRCT) for any changes suggestive of COVID-19; surrogate laboratory parameters such as C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), or interleukin-6 (IL-6) for assessing the severity of the disease; and other organ-specific tests to identify the multiorgan involvement in severe-to-critical COVID-19. Chest computed tomography (CT) scans play a significant role in the management of COVID-19 disease and serve as an indicator of disease severity and its possible outcome, which might help in the early identification of patients who might need critical care and earlier prognostication. METHODS: A retrospective observational study was conducted at a single center in a level 3 critical care unit (CCU) of a 750-bed teaching hospital in Hyderabad, Telangana, India, over a period of six months. All RT-PCR-positive COVID-19 patients admitted to the CCU with CT chest performed within 24 hours of admission were screened for eligibility for this study. CT severity scoring was based on chest HRCT or CT. RESULTS: Of the 110 patients, a majority (36.36%) were aged between 61 and 70 years. The mean age of our study population was 59.65±11.88 years. Of the 110 patients, the majority were admitted to the hospital for 22-28 days (24.55%), followed by 8-14 days (22.72%), and 21.82% were admitted for one day. Of the 110 patients, a majority were admitted to the CCU for seven days (41.82%), followed by 15-21 days (24.55%); and 19.09% were admitted for 8-14 days. Most of the patients were discharged (65.45%), and we had a 34.55% mortality rate in our study. We found a significant association between chest CT severity score (CTSS) and the age of the patient, duration of hospital stay, and duration of CCU stay using multivariate regression analysis. CONCLUSION: CTSS could be greatly helpful for the screening and early identification of the disease, especially in those patients awaiting an RT-PCR report or with negative RT-PCR, which would lead to appropriate isolation and treatment measures. Early detection could also help assess the progression of the disease, alter the course of management at the earliest point possible, and improve the prognostication of COVID-19 patients.

3.
Laryngoscope ; 134 Suppl 4: S1-S11, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37540033

RESUMO

OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short- versus long-term exposure to intermittent hypoxia (IH) on pro-inflammatory mediators within vulnerable organs impacted by OSA. STUDY DESIGN: Experimental animal study. METHODS: A total of 8-10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short-term) or 6 weeks (long-term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro-inflammatory mediators from peripheral tissues. RESULTS: We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short-term exposure to IH. Although there were tissue-specific alterations in the gene expression of pro-inflammatory mediators, with down-regulation in the lung and up-regulation in the heart, we also observed reduced protein levels of pro-inflammatory mediators in the serum, lung, and heart following short-term exposure to IH. Long-term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart. CONCLUSIONS: We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs. LEVEL OF EVIDENCE: NA Laryngoscope, 134:S1-S11, 2024.


Assuntos
Hipóxia , Apneia Obstrutiva do Sono , Camundongos , Animais , Camundongos Endogâmicos C57BL , Hipóxia/patologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Modelos Animais de Doenças
4.
F1000Res ; 12: 762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576540

RESUMO

Background: The natural day-night cycle synchronizes our circadian rhythms, but modern work practices like night shifts disrupt this pattern, leading to increased exposure to nighttime light. This exposure is linked to various health issues. While some studies have explored the effects of night shifts on human circadian rhythms, there is limited research on the consequences of long-term exposure to shift-work light conditions. Rodents can provide valuable insights into these effects. This study aimed to examine how short- or long-term exposure to rotating shifts and chronic jetlag affects the core circadian oscillators in the liver and skin of mammals. Methods: C57BL/6J male mice were subjected to simulated shift-work light conditions, including short-term or long-term rotating shifts and chronic jet-lag conditions. Liver and skin samples were collected every four hours over a 24-hour period on the second day of constant darkness. RNA was extracted and qRT-PCR analysis was conducted to measure the circadian gene expression in liver and skin tissues. Circadian rhythm analysis using CircaCompare compared the control group to mice exposed to shift-work light conditions. Results: The liver's circadian clock is significantly altered in mice under long-term rotating shift conditions, with a lesser but still noticeable impact in mice experiencing chronic jetlag. However, short-term rotating shift conditions do not significantly affect the liver's circadian clock. Conversely, all three simulated shift conditions affect the skin's circadian clock, indicating that the skin clock is more sensitive to shift-work light conditions than the liver clock. Compared to the liver, the skin's circadian clock is greatly affected by long-term rotating shift conditions. Conclusions: The study findings indicate more pronounced disturbances in the canonical clock genes of the skin compared to the liver under simulated shift-work light conditions. These results suggest that the skin clock is more vulnerable to the effects of shift-work.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Animais , Masculino , Camundongos , Relógios Circadianos/genética , Ritmo Circadiano/genética , Modelos Animais de Doenças , Fígado , Mamíferos , Camundongos Endogâmicos C57BL
5.
PLoS Biol ; 21(5): e3002139, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37252926

RESUMO

Intermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately associated with stabilization of hypoxia-inducible factors (HIFs) under hypoxic conditions. In patients, IH occurs during the sleep phase of the 24-hour sleep-wake cycle, potentially affecting their circadian rhythms. Alterations in the circadian clock have the potential to accelerate pathological processes, including other comorbid conditions that can be associated with chronic, untreated OSA. We hypothesized that changes in the circadian clock would manifest differently in those organs and systems known to be impacted by OSA. Using an IH model to represent OSA, we evaluated circadian rhythmicity and mean 24-hour expression of the transcriptome in 6 different mouse tissues, including the liver, lung, kidney, muscle, heart, and cerebellum, after a 7-day exposure to IH. We found that transcriptomic changes within cardiopulmonary tissues were more affected by IH than other tissues. Also, IH exposure resulted in an overall increase in core body temperature. Our findings demonstrate a relationship between early exposure to IH and changes in specific physiological outcomes. This study provides insight into the early pathophysiological mechanisms associated with IH.


Assuntos
Apneia Obstrutiva do Sono , Transcriptoma , Animais , Camundongos , Transcriptoma/genética , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/patologia , Ritmo Circadiano/genética , Modelos Animais de Doenças , Hipóxia/metabolismo
6.
PLoS One ; 18(5): e0284824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37141220

RESUMO

Neurons in the hypothalamic preoptic area (POA) regulate multiple homeostatic processes, including thermoregulation and sleep, by sensing afferent input and modulating sympathetic nervous system output. The POA has an autonomous circadian clock and may also receive circadian signals indirectly from the suprachiasmatic nucleus. We have previously defined a subset of neurons in the POA termed QPLOT neurons that are identified by the expression of molecular markers (Qrfp, Ptger3, LepR, Opn5, Tacr3) that suggest receptivity to multiple stimuli. Because Ptger3, Opn5, and Tacr3 encode G-protein coupled receptors (GPCRs), we hypothesized that elucidating the G-protein signaling in these neurons is essential to understanding the interplay of inputs in the regulation of metabolism. Here, we describe how the stimulatory Gs-alpha subunit (Gnas) in QPLOT neurons regulates metabolism in mice. We analyzed Opn5cre; Gnasfl/fl mice using indirect calorimetry at ambient temperatures of 22°C (a historical standard), 10°C (a cold challenge), and 28°C (thermoneutrality) to assess the ability of QPLOT neurons to regulate metabolism. We observed a marked decrease in nocturnal locomotion of Opn5cre; Gnasfl/fl mice at both 28°C and 22°C, but no overall differences in energy expenditure, respiratory exchange, or food and water consumption. To analyze daily rhythmic patterns of metabolism, we assessed circadian parameters including amplitude, phase, and MESOR. Loss-of-function GNAS in QPLOT neurons resulted in several subtle rhythmic changes in multiple metabolic parameters. We observed that Opn5cre; Gnasfl/fl mice show a higher rhythm-adjusted mean energy expenditure at 22°C and 10°C, and an exaggerated respiratory exchange shift with temperature. At 28°C, Opn5cre; Gnasfl/fl mice have a significant delay in the phase of energy expenditure and respiratory exchange. Rhythmic analysis also showed limited increases in rhythm-adjusted means of food and water intake at 22°C and 28°C. Together, these data advance our understanding of Gαs-signaling in preoptic QPLOT neurons in regulating daily patterns of metabolism.


Assuntos
Regulação da Temperatura Corporal , Hipotálamo , Animais , Camundongos , Regulação da Temperatura Corporal/fisiologia , Ritmo Circadiano/fisiologia , Metabolismo Energético , Homeostase , Hipotálamo/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Opsinas/metabolismo , Temperatura
7.
J Cancer Res Ther ; 18(6): 1811-1813, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412451

RESUMO

Solitary bone metastasis in endometrial cancer is very rare. We report a young 29-year-old nulliparous female of endometrial cancer who developed solitary humerus metastasis after 8 months of primary treatment of surgery and adjuvant radiotherapy and chemotherapy. She was treated with local radiotherapy and combination chemotherapy and bisphosphonates. At 6 months follow-up the patient is doing well and is asymptomatic. Even though rare, keeping a high index of suspicion and sincere evaluation in patients on follow-up presenting with bone pains can detect early recurrences. Timely start of multimodality treatment helps relieve symptoms and improves quality of life.


Assuntos
Neoplasias do Endométrio , Radioterapia (Especialidade) , Humanos , Feminino , Adulto , Qualidade de Vida , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Úmero , Terapia Combinada
8.
Toxicol Appl Pharmacol ; 436: 115863, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34998857

RESUMO

Solid tumors are commonly treated with cisplatin, which can cause off-target side effects in cancer patients. Chronotherapy is a potential strategy to reduce drug toxicity. To determine the effectiveness of timed-cisplatin treatment in mammals, we compared two conditions: clock disrupted jet-lag and control conditions. Under normal and disrupted clock conditions, triple-negative mammary carcinoma cells were injected subcutaneously into eight-week-old NOD.Cg-Prkdcscid/J female mice. Tumor volumes and body weights were measured in these mice before and after treatment with cisplatin. We observed an increase in tumor volumes in mice housed under disrupted clock compared to the normal clock conditions. After treatment with cisplatin, we observed a reduced tumor growth rate in mice treated at ZT10 compared to ZT22 and untreated cohorts under normal clock conditions. However, these changes were not seen with the jet-lag protocol. We also observed greater body weight loss in mice treated with ZT10 compared to ZT22 or untreated mice in the jet-lag protocol. Our observations suggest that the effectiveness of cisplatin in mammary carcinoma treatment is time-dependent in the presence of the circadian clock.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cronoterapia/efeitos adversos , Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Cisplatino/efeitos adversos , Cisplatino/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Animais , Linhagem Celular , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos NOD
9.
Saudi J Kidney Dis Transpl ; 33(3): 404-412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37843141

RESUMO

Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19), and its severity is linked to the adverse outcomes of multiorgan involvement. We attempted to assess the clinical outcomes and determinants of mortality in patients admitted to our COVID-19 care center from May to November 2020 who developed AKI through a retrospective examination of their case records. The data of those who developed AKI were analyzed for their clinical parameters, clinical presentation, history, laboratory parameters, urine output measurements, requirements for dialysis, treatment, and treatment outcomes (discharge or death). These outcomes were correlated to the comorbidities, laboratory parameters, the Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, sequential organ failure assessment score, and need for dialysis or renal replacement therapy. Of 1890 patients admitted, 132 (6.98%) patients developed AKI. Of 450 deaths from all causes, 67 (14%) were in AKI patients. There were 100 (75.8%) males and 32 (24.8%) females. The mean age was 62.05 ± 11.48 years. The median duration of stay was 7 days (interquartile range: 4--11.75 days). The number of patients in AKI Stages 1, 2, and 3 was 1 (0.75%), 64 (48.48%), and 67 (50.75%), respectively. The most common symptoms were breathlessness (85.6%), fever (84.5%), myalgia (81.19%), and weakness (76.5%). Multivariate analysis showed that the determinants of mortality were a partial pressure of oxygen saturation (pO2) of <75% and of 76%-85% compared with a pO2 of >85%, not receiving remdesivir, and KDIGO Stage >2.


Assuntos
Injúria Renal Aguda , COVID-19 , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , COVID-19/complicações , COVID-19/terapia , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Injúria Renal Aguda/etiologia , Mortalidade Hospitalar , Fatores de Risco
10.
Genes (Basel) ; 12(10)2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34681021

RESUMO

At least one-third of adults in the United States experience intermittent hypoxia (IH) due to health or living conditions. The majority of these adults suffer with sleep breathing conditions and associated circadian rhythm disorders. The impact of IH on the circadian clock is not well characterized. In the current study, we used an IH mouse model to understand the impact of IH on the circadian gene expression of the canonical clock genes in the central (the brain) and peripheral (the liver) tissues. Gene expression was measured using a Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). CircaCompare was used to evaluate the differential rhythmicity between normoxia and IH. Our observations suggested that the circadian clock in the liver was less sensitive to IH compared to the circadian clock in the brain.


Assuntos
Proteínas CLOCK/genética , Ritmo Circadiano/genética , Hipóxia/genética , Sono/genética , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Relógios Circadianos/genética , Relógios Circadianos/fisiologia , Regulação da Expressão Gênica/genética , Humanos , Hipóxia/fisiopatologia , Fígado/metabolismo , Fígado/fisiologia , Camundongos , Sono/fisiologia
11.
Diagnostics (Basel) ; 11(6)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199193

RESUMO

Obstructive sleep apnea (OSA) is a complex process that can lead to the dysregulation of the molecular clock, as well as 24 h rhythms of sleep and wake, blood pressure, and other associated biological processes. Previous work has demonstrated crosstalk between the circadian clock and hypoxia-responsive pathways. However, even in the absence of OSA, disrupted clocks can exacerbate OSA-associated outcomes (e.g., cardiovascular or cognitive outcomes). As we expand our understanding of circadian biology in the setting of OSA, this information could play a significant role in the diagnosis and treatment of OSA. Here, we summarize the pre-existing knowledge of circadian biology in patients with OSA and examine the utility of circadian biomarkers as alternative clinical tools.

12.
J Clin Sleep Med ; 17(12): 2533-2541, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34176557

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a chronic and widely prevalent disease associated with multiple health disorders. Current diagnostic strategies for OSA are limited because of cost, time, and access. Epigenetic signatures offer insight into the relationships between disease and environment and could play a significant role in developing both diagnostic and therapeutic tools for OSA. In the current study, a systematic literature search was conducted to investigate the existing evidence of OSA-associated epigenetic modifications. METHODS: A systematic literature search was performed using electronic academic databases including PubMed, CINAHL, Scopus, Embase, EBM Reviews, and Web of Science. However, the current study focused on screening for original, English-language articles pertaining to OSA and associated epigenetic mechanisms. To produce unbiased results, screening was performed independently by authors. RESULTS: We identified 2,944 publications in our systematic search. Among them, 65 research articles were related to OS A-associated differential gene expression, genetic variation, and epigenetic modifications. Although these 65 articles were considered for full manuscript review, only 12 articles met the criteria of OSA-associated epigenetic modifications in human and animal models. Human patients with OSA had unique epigenetic changes compared to healthy control patients and, interestingly, epigenetic signatures were commonly identified in genes associated with metabolic and inflammatory pathways. CONCLUSIONS: Although the available studies are limited, this research provides novel insights for the development of epigenetic markers for the diagnosis and treatment of OSA. Thorough genome-wide investigations will be required to develop cost-effective, robust biomarkers for the identification of OSA among children and adults. Here, we offer a study design for such efforts. CITATION: Leader BA, Koritala BSC, Moore CA, Dean EG, Kottyan LC, Smith DF. Epigenetics of obstructive sleep apnea syndrome: a systematic review. J Clin Sleep Med. 2021;17(12):2533-2541.


Assuntos
Apneia Obstrutiva do Sono , Biomarcadores , Análise Custo-Benefício , Epigênese Genética , Humanos , Apneia Obstrutiva do Sono/genética
13.
Pigment Cell Melanoma Res ; 34(5): 955-965, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34160901

RESUMO

Solar ultraviolet B radiation (UVB) is one of the leading causes of various skin conditions, including photoaging, sunburn erythema, and melanoma. As a protective response, the skin has inbuilt defense mechanisms, including DNA repair, cell cycle, apoptosis, and melanin synthesis. Though DNA repair, cell cycle, and apoptosis are clock controlled, the circadian mechanisms associated with melanin synthesis are not well understood. Using human melanocytes and melanoma cells under synchronized clock conditions, we observed that the microphthalmia-associated transcription factor (MITF), a rate-limiting protein in melanin synthesis, is expressed rhythmically with 24-hr periodicity in the presence of circadian clock protein, BMAL1. Furthermore, we demonstrated that BMAL1 binds to the promoter region of MITF and transcriptionally regulates its expression, which positively influences melanin synthesis. Finally, we report that an increase in melanin levels due to BMAL1 overexpression protects human melanoma cells from UVB. In conclusion, our studies provide novel insights into the mechanistic role of the circadian clock in melanin synthesis and protection against UVB-mediated DNA damage and genomic instability.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição ARNTL/genética , Animais , Humanos , Melanoma/genética , Melanoma/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Proteínas de Neoplasias/genética
14.
J Pineal Res ; 70(3): e12726, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33638890

RESUMO

Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24-hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.


Assuntos
Biomarcadores Tumorais/genética , Transtornos Cronobiológicos/etiologia , Ritmo Circadiano , Dano ao DNA , Reparo do DNA , Neoplasias/etiologia , Jornada de Trabalho em Turnos/efeitos adversos , Transcriptoma , Ciclos de Atividade , Adulto , Transtornos Cronobiológicos/genética , Transtornos Cronobiológicos/fisiopatologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias/genética , Neoplasias/patologia , Medição de Risco , Fatores de Risco , Sono , Fatores de Tempo , Adulto Jovem
15.
J Control Release ; 329: 76-86, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33245955

RESUMO

Nano-formulations that are responsive to tumour-related and externally-applied stimuli can offer improved, site-specific antitumor effects, and can improve the efficacy of conventional therapeutic agents. Here, we describe the performance of a novel stimulus-responsive nanoparticulate platform for the targeted treatment of prostate cancer using sonodynamic therapy (SDT). The nanoparticles were prepared by self-assembly of poly(L-glutamic acid-L-tyrosine) co-polymer with hematoporphyrin. The nanoparticulate formulation was characterized with respect to particle size, morphology, surface charge and singlet oxygen production during ultrasound exposure. The response of the formulation to the presence of cathepsin B, a proteolytic enzyme that is overexpressed and secreted in the tumour microenvironment of many solid tumours, was assessed. Our results showed that digestion with cathepsin B led to nanoparticle size reduction. In the absence of ultrasound, the formulation exhibited greater toxicity at acidic pH than at physiological pH, using the human prostate cells lines LNCaP and PC3 as targets. Nanoparticle cellular uptake was enhanced at acidic pH - a condition that was also associated with greater cathepsin B production. Nanoparticles exhibited enhanced ultrasound-induced cytotoxicity against both prostate cancer cell lines. Subsequent proof-of-concept in vivo studies demonstrated that, when ectopic human xenograft LNCaP tumours in SCID mice were treated with SDT using the systemically-administered nanoparticulate formulation at a single dose, tumour volumes decreased by up to 64% within 24 h. No adverse effects were observed in the nanoparticle-treated mice and their body weight remained stable. The potential of this novel formulation to deliver safe and effective treatment of prostate cancer is discussed.


Assuntos
Nanopartículas , Neoplasias da Próstata , Animais , Catepsina B , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos SCID , Microambiente Tumoral
16.
J Biol Rhythms ; 35(2): 134-144, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31878828

RESUMO

The circadian clock controls daily activities at the cellular and organismic level, allowing an organism to anticipate incoming stresses and to use resources accordingly. The circadian clock has therefore been considered a fitness trait in multiple organisms. However, the mechanism of how circadian clock variation influences organismal reproductive fitness is still not well understood. Here we describe habitat-specific clock variation (HSCV) of asexual reproduction in Neurospora discreta, a species that is adapted to 2 different habitats, under or above tree bark. African (AF) N. discreta strains, whose habitat is above the tree bark in light-dark (LD) conditions, display a higher rhythmicity index compared with North American (NA) strains, whose habitat is under the tree bark in constant dark (DD). Although AF-type strains demonstrated an overall fitness advantage under LD and DD conditions, NA-type strains exhibit a habitat-specific fitness advantage in DD over the LD condition. In addition, we show that allelic variation of the clock-controlled gene, Ubiquinol cytochrome c oxidoreductase (NEUDI_158280), plays a role in HSCV by modulating cellular reactive oxygen species levels. Our results demonstrate a mechanism by which local adaptation involving circadian clock regulation influences reproductive fitness.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano , Ecossistema , Aptidão Genética , Neurospora/fisiologia , Reprodução Assexuada/genética , Adaptação Fisiológica , Alelos , Proteínas CLOCK/genética , Relógios Circadianos/fisiologia , Neurospora/genética , Fotoperíodo
17.
Hum Exp Toxicol ; 38(10): 1195-1211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31256688

RESUMO

The present study was premeditated to examine the radioprotective effects of aqueous Aloe vera gel extract against whole-body X-ray irradiation-induced hematological alterations and splenic tissue injury in mice. Healthy male balb/c mice were divided into four groups: group 1, control; group 2, A. vera (50 mg/kg body weight) administered per oral on alternate days for 30 days (15 times); group 3, X-ray exposure of 2 Gy (0.25 Gy twice a day for four consecutive days in the last week of the experimental protocol); and group 4, A. vera + X-ray. X-ray exposure caused alterations in histoarchitecture of spleen along with enhanced clastogenic damage as assessed by micronucleus formation and apoptotic index. Irradiation caused an elevation in proinflammatory cytokines like tumor necrosis factor and interleukin-6, total leucocyte counts, neutrophil counts and decreased platelet counts along with unaltered red blood cell counts and hemoglobin. Irradiation also caused an elevation in reactive oxygen species (ROS), lipid peroxidation (LPO) levels, lactate dehydrogenase activity and alterations in enzymatic and nonenzymatic antioxidant defense mechanism in plasma and spleen. However, administration of A. vera gel extract ameliorated X-ray irradiation-induced elevation in ROS/LPO levels, histopathological and clastogenic damage. It also modulated biochemical indices, inflammatory markers, and hematological parameters. These results collectively indicated that the A. vera gel extract offers protection against whole-body X-ray exposure by virtue of its antioxidant, anti-inflammatory and anti-apoptotic potential.


Assuntos
Apoptose/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Preparações de Plantas/farmacologia , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/prevenção & controle , Baço/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/metabolismo , Apoptose/efeitos da radiação , Contagem de Leucócitos , Leucócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Contagem de Plaquetas , Lesões Experimentais por Radiação/patologia , Baço/patologia , Baço/efeitos da radiação , Irradiação Corporal Total
18.
Psych J ; 7(4): 176-196, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30456783

RESUMO

In the course of evolution, health is prioritized for human well-being and economies. Epidemiological and experimental studies suggest that modern life habits, including eating habits, and living and working conditions, can deteriorate health through circadian misalignment. This has been most commonly observed with urban societies and working classes of non-standard working schedules (NSWSs), such as shift work, night work, and overtime work. Poor health conditions with NSWSs generate economic burden for the modern society. Therefore, we attempt to provide a systematic approach to understanding the relations among the circadian clock, health, and economics. To understand these connections, we review the mechanisms of the human circadian clock and how modern living conditions can misalign the circadian system and associated health consequences. We also emphasize the importance of health for the modern economy and the economic costs of health disorders associated with circadian disruption and NSWSs.


Assuntos
Relógios Circadianos/fisiologia , Economia , Nível de Saúde , Ritmo Circadiano/fisiologia , Emprego , Humanos , Luz , Jornada de Trabalho em Turnos
19.
Curr Health Sci J ; 44(4): 374-380, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31123615

RESUMO

Polycystic kidney disease represented by autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) have a major impact of mortality in children. We conducted a study of a premature infant with an estimated gestation date of 32 weeks with a presumptive prenatal diagnosis of right polycystic kidney. A 28-year-old primigravida with pre-eclampsia was admitted at the gynecology unit of Clinical Emergency County Hospital of Craiova. The clinical examination revealed a large abdominal distention due probably to the right polycystic kidney, suspected on prenatal ultrasound and radiography. The preterm neonate undergone right nephrectomy 5 days after birth. Histopathology of the kidney was performed in the Pathology Department of the Emergency County Hospital of Craiova and in the Center for Microscopic Morphology and Immunology of U.M.F. of Craiova. Microscopy revealed dilated cysts lined by simple cuboidal or flattened epithelium, and islets of remnant kidney parenchyma separated by edematous stroma. Immunohistochemistry for CD34 revealed incomplete blood arcades which did not seem to be in contact with all the tubular elements of the parenchyma, when compared to a control age-matched kidney. The patient had a favorable postoperative evolution, she was clinically stable on discharge from the hospital with a follow-up strategy including genetic testing.

20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-780402

RESUMO

@#Physical Activity Scale for the Elderly (PASE) is a simple, valid and reliable questionnaire that can be administered to quantify older adults’ physical activity levels during daily living. However, PASE in Malay language for use among older population is not available. The objective of our current study was to evaluate the reliability and validity of the Malay translated Physical Activity Scale for Elderly (PASE-M) for the use among older adults. Objective results of physical activity were obtained by wearing continuously an accelerometer for one week among a population of older adults in Malaysia who speak Malay language. Participants completed PASE-M twice, on day-8 (PASE-M1) and day-15 (PASE-M2). Concurrent validity between PASE-M1 and accelerometer results was assessed using Spearman’s rank correlation coefficient. Test-retest reliability for one week interval of PASE-M was tested using Spearman’s rank correlation coefficient and Intra-class correlation coefficients (ICC). Forty-four community-dwelling older adults (12 men and 32 women; mean age ± SD= 66.95 ± 5.34) participated in this study. However, only 33 participants (8 men and 25 women; mean age ± SD= 66.64 ± 5.51) were able to achieve the minimum accelerometer wearing time and filled up the PASE-M questionnaire for two times with one weeks interval. The results showed the PASE-M score was significantly correlated with vector magnitude (VM) counts (r=0.54, p<0.01), time in moderate-to-vigorous physical activity (MVPA) (r =0.55, p<0.01), energy expenditure (r =0.53, p<0.01) and walking steps (r=0.39, p<0.05). A high reliability (ICC = 0.96) was demonstrated between first and the subsequent administration of PASE-M (p<0.01, 95% CI: 0.92-0.98). The PASE-M is a valid and reliable questionnaire to assess physical activity level for Malaysian community-dwelling older adults.

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