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Five small interfering RNA (siRNA)-based therapeutics have been approved by the Food and Drug Administration (FDA), namely patisiran, givosiran, lumasiran, inclisiran, and vutrisiran. Besides, siRNA delivery to the target site without toxicity is a big challenge for researchers, and naked-siRNA delivery possesses several challenges, including membrane impermeability, enzymatic degradation, mononuclear phagocyte system (MPS) entrapment, fast renal excretion, endosomal escape, and off-target effects. The siRNA therapeutics can silence any disease-specific gene, but their intracellular and extracellular barriers limit their clinical applications. For this purpose, several modifications have been employed to siRNA for better transfection efficiency. Still, there is a quest for better delivery systems for siRNA delivery to the target site. In recent years, nanoparticles have shown promising results in siRNA delivery with minimum toxicity and off-target effects. Patisiran is a lipid nanoparticle (LNP)-based siRNA formulation for treating hereditary transthyretin-mediated amyloidosis that ultimately warrants the use of nanoparticles from different classes, especially lipid-based nanoparticles. These nanoparticles may belong to different categories, including lipid-based, polymer-based, and inorganic nanoparticles. This review briefly discusses the lipid, polymer, and inorganic nanoparticles and their sub-types for siRNA delivery. Finally, several clinical trials related to siRNA therapeutics are addressed, followed by the future prospects and conclusions.
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Neuropatias Amiloides Familiares , Nanopartículas , Polímeros , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transfecção , LipídeosRESUMO
Assessing the relative importance of climate change and human activities is important in developing sustainable management policies for regional land use. In this study, multiple remote sensing datasets, i.e. CHIRPS (Climate Hazard Group InfraRed Precipitation with Station Data) precipitation, MODIS Land Surface Temperature (LST), Enhanced Vegetation Index (EVI), Potential Evapotranspiration (PET), Soil Moisture (SM), WorldPop, and nighttime light have been analyzed to investigate the effect that climate change (CC) and regional human activities (HA) have on vegetation dynamics in eastern India for the period 2000 to 2022. The relative influence of climate and anthropogenic factors is evaluated on the basis of non-parametric statistics i.e., Mann-Kendall and Sen's slope estimator. Significant spatial and elevation-dependent variations in precipitation and LST are evident. Areas at higher elevations exhibit increased mean annual temperatures (0.22 °C/year, p < 0.05) and reduced winter precipitation over the last two decades, while the northern and southwest parts of West Bengal witnessed increased mean annual precipitation (17.3 mm/year, p < 0.05) and a slight cooling trend. Temperature and precipitation trends are shown to collectively impact EVI distribution. While there is a negative spatial correlation between LST and EVI, the relationship between precipitation and EVI is positive and stronger (R2 = 0.83, p < 0.05). Associated hydroclimatic parameters are potent drivers of EVI, whereby PET in the southwestern regions leads to markedly lower SM. The relative importance of CC and HA on EVI also varies spatially. Near the major conurbation of Kolkata, and confirmed by nighttime light and population density data, changes in vegetation cover are very clearly dominated by HA (87%). In contrast, CC emerges as the dominant driver of EVI (70-85%) in the higher elevation northern regions of the state but also in the southeast. Our findings inform policy regarding the future sustainability of vulnerable socio-hydroclimatic systems across the entire state.
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Mudança Climática , Índia , Atividades Humanas , Humanos , Chuva , Temperatura , Monitoramento AmbientalRESUMO
The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently approved vaccines for COVID-19 are engendering hope, finding new ways to cure the viral pandemic is still a quest for researchers worldwide. Major pandemics in history have been of viral origin, such as SARS, MERS, H1NI, Spanish flu, and so on. A larger emphasis has been on discovering potential vaccines, novel antiviral drugs, and agents that can mitigate the viral infection symptoms; however, a relatively new area, RNA interference (RNAi), has proven effective as an antiviral agent. The RNAi phenomenon has been largely exploited to cure cancer, neurodegenerative diseases, and some rare diseases. The U.S. Food and Drug Administration has recently approved three siRNA products for human use that garner significant hope in siRNA therapeutics for coronaviruses. There have been some commentaries and communications addressing this area. We have summarized and illustrated the significance and the potential of the siRNA therapeutics available as of April 30, 2021 to combat the ongoing viral pandemic and the emerging new variants such as B.1.1.7 and B.1.351. Numerous successful in vitro studies and several investigations to address the clinical application of siRNA therapeutics provide great hope in this field. This seminal Review describes the significance of siRNA-based therapy to treat diverse viral infections in addition to the current coronavirus challenge. In addition, we have thoroughly reviewed the patents approved for coronaviruses, the major challenges in siRNA therapy, and the potential approaches to address them, followed by innovation and prospects.
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Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pandemias/prevenção & controle , RNA Interferente Pequeno/uso terapêutico , SARS-CoV-2/genética , Antivirais/história , COVID-19/epidemiologia , COVID-19/história , COVID-19/virologia , Ensaios Clínicos como Assunto , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , História do Século XX , História do Século XXI , Humanos , Mutação , Patentes como Assunto , RNA Interferente Pequeno/história , SARS-CoV-2/patogenicidadeRESUMO
A simple and sensitive flow injection-chemiluminescence (FI-CL) method was developed for determination of cetirizine dihydrochloride (CTZH) in pharmaceuticals. The method is primarily based on the enhancement effect of CTZH on the tris(2,2'-bipyridyl)ruthenium (II)-diperiodatoargentate (III) ([Ru(bpy)3 ]2+ -Ag(III) complex) CL system in an acidic medium. The optimum investigated variables of the CL reaction were: [Ru(bpy)3 ]2+ , 50 × 10-6 mol/L; sulfuric acid, 1.0 × 10-3 mol/L; Ag(III) complex, 100 × 10-6 mol/L; potassium hydroxide, 1.0 × 10-3 mol/L; flow rate, 3.0 ml/min and sample loop volume, 300 µl. The detection and quantification limits were 2.0 × 10-4 and 5.0 × 10-4 mg/L (S/N of 3 and 10) respectively with a linear calibration range of 5.0 × 10-4 to 7.5 mg/L (R2 = 0.9999, n = 11), injection throughput of 110/h and the relative standard deviations of 1.5-3.5% over the range studied. The methodology was successfully applied to determine CTZH in different pharmaceutical samples and validated with a high-performance liquid chromatography method, and resulted in the recovery of 94.6-108.6%. The probable CL reaction mechanism is described in brief.
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Preparações Farmacêuticas , Rutênio , 2,2'-Dipiridil , Cetirizina , Análise de Injeção de Fluxo , Luminescência , Medições Luminescentes , PrataRESUMO
Practical biodiversity conservation relies on delineation of biologically meaningful units. Manta and devil rays (Mobulidae) are threatened worldwide, yet morphological similarities and a succession of recent taxonomic changes impede the development of an effective conservation strategy. Here, we generate genome-wide single nucleotide polymorphism (SNP) data from a geographically and taxonomically representative set of manta and devil ray samples to reconstruct phylogenetic relationships and evaluate species boundaries under the general lineage concept. We show that nominal species units supported by alternative data sources constitute independently evolving lineages, and find robust evidence for a putative new species of manta ray in the Gulf of Mexico. Additionally, we uncover substantial incomplete lineage sorting indicating that rapid speciation together with standing variation in ancestral populations has driven phylogenetic uncertainty within Mobulidae. Finally, we detect cryptic diversity in geographically distinct populations, demonstrating that management below the species level may be warranted in certain species. Overall, our study provides a framework for molecular genetic species delimitation that is relevant to wide-ranging taxa of conservation concern, and highlights the potential for genomic data to support effective management, conservation and law enforcement strategies.
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Biodiversidade , Genoma , Golfo do México , FilogeniaRESUMO
BACKGROUND: The WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP Verpolin homologous) family of proteins are structurally related and responsible for regulation of actin polymerization through their interaction with actin related proteins 2&3 (ARP 2/3). WAVE-3 has exhibited an association with disease progression and poorer prognosis of certain malignancies. In the current study, we determined the role of WAVE-3 in hepatocyte growth factor induced cellular changes including cell matrix interaction, invasion and cellular motility, and pathways that may be responsible for the changes in prostate cancer cells. METHODS: We used hammer head ribozymes to knock down the expression of WAVE-3 in PC-3 prostate cancer cell line. In vitro cellular functional assays including growth, invasion, adhesion, motility and invasion, were performed to assess the effects of WAVE-3 knock down. Further experimentation was performed to investigate the role of different pathway through expression and phosphorylation status of various intermediate proteins. RESULTS: WAVE-3 knockdown reduced invasive potential and motility of prostate cancer cells. Following addition of HGF, control cells showed significantly increased invasion and motility (p value <0.5) and marked increase in cellular growth. However, WAVE-3 knockdown cell line failed to show any increase in these trends (p value <0.5) except increased growth compared with control cells. Further experiments revealed that HGF-induced activation of Paxillin was weakened by the knockdown of WAVE-3. Our study also indicated that reduced invasiveness following WAVE-3 knockdown, may be related to reduce activity of MMP-2. CONCLUSIONS: Our studies suggest a vital role of WAVE-3 in HGF induced invasion and migration in which Paxillin and MMP-2 are involved. Further study will shed light on its potential as therapeutic target to suppress local invasion and metastasis of prostate cancer cells.
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Terminology is pivotal for facilitating clear communication and minimizing ambiguity, especially in specialized fields such as chemistry. In materials science, a subset of chemistry, the term "pore" is traditionally linked to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, which categorizes pores into "micro", "meso", and "macro" based on size. However, applying this terminology in closely-related areas, such as 3D bioprinting, often leads to confusion owing to the lack of consensus on specific definitions and classifications tailored to each field. This review article critically examines the current use of pore terminology in the context of 3D bioprinting, highlighting the need for reassessment to avoid potential misunderstandings. We propose an alternative classification that aligns more closely with the specific requirements of bioprinting, suggesting a tentative size-based division of interconnected pores into 'parvo'-(d < 25 µm), 'medio'-(25 < d < 100 µm), and 'magno'-(d > 100 µm) pores, relying on the current understanding of the pore size role in tissue formation. The introduction of field-specific terminology for pore sizes in 3D bioprinting is essential to enhance the clarity and precision of research communication. This represents a step toward a more cohesive and specialized lexicon that aligns with the unique aspects of bioprinting and tissue engineering.
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Background: This is one of the first studies exploring immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blue-collar workers in Abu Dhabi. Aims: This study estimated the seroprevalence of SARS-CoV-2 infection among workers living in a closed setting using qualitative analysis of the total SARS CoV-2 antibody immune response. Methods: We conducted this monocentric, prospective, observational study in a labour compound for a cohort of workers between 28 March and 6 July 2020. We tested for SARS-CoV-2 (nasopharyngeal) (RT-PCR) and anti-SARS-CoV-2 T-Ab. Results: Out of a total of 1600 workers, 1206 (75.0%) participated in the study - all were males, median age 35 years (19-63 years). We found 51% of the participants to be positive for SARS-CoV-2; the 49.0% who tested negative were considered as contacts. Anti-SARS-CoV-2 T-Ab was detected among 864 participants, showing an overall point prevalence of 71.6%. A relatively higher response was found among cases (89.0%) than among contacts (53.2%). Conclusion: This study highlights the need to prioritize public health interventions in closed settings where disease transmission is higher due to greater overall exposure. A high seroprevalence of anti-SARS-CoV-2 T-Ab was found among the residents. A serial quantitative study applying time series and regression models is recommended to further evaluate the sustainability of the immune response among this and similar population groups.
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COVID-19 , Masculino , Humanos , Adulto , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Emirados Árabes Unidos/epidemiologia , Estudos Soroepidemiológicos , Estudos Prospectivos , Anticorpos Antivirais , Pessoal de SaúdeRESUMO
Gelatin-based hydrogels have emerged as a popular scaffold material for tissue engineering applications. The introduction of variable crosslinking methods has shown promise for fabricating stable cell-laden scaffolds. In this work, we examine promising composite biopolymer-based inks for extrusion-based 3D bioprinting, using a dual crosslinking approach. A combination of carefully selected printable hydrogel ink compositions and the use of photoinduced covalent and ionic crosslinking mechanisms allows for the fabrication of scaffolds of high accuracy and low cytotoxicity, resulting in unimpeded cell proliferation, extracellular matrix deposition, and mineralization. Three selected bioink compositions were characterized and the respective cell-laden scaffolds were bioprinted. Temporal stability, morphology, swelling, and mechanical properties of the scaffolds were thoroughly studied and the biocompatibility of the constructs was assessed using rat mesenchymal stem cells while focusing on osteogenesis. Experimental results showed that the composition of 1% alginate, 4% gelatin, and 5% (w/v) gelatine methacrylate, was found to be optimal among the examined, with shape fidelity of 88%, large cell spreading area and cell viability at around 100% after 14 days. The large pore diameters that exceed 100 µm, and highly interconnected scaffold morphology, make these hydrogels extremely potent in bone tissue engineering and bone organoid fabrication.
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The Modified Fournier Index (MFI) is one of the indices that can assess the erosivity of rainfall. However, the implementation of the artificial neural network (ANN) for the prediction of the MFI is still rare. In this research, climate data (monthly and yearly precipitation (pi, Ptotal) (mm), daily maximum precipitation (Pd-max) (mm), monthly mean temperature (Tavg) (°C), daily maximum mean temperature (Td-max) (°C), and daily minimum mean temperature (Td-min) (°C)) were collected from three stations in Hungary (Budapest, Debrecen, and Pécs) between 1901 and 2020. The MFI was calculated, and then, the performance of two ANNs (multilayer perceptron (MLP) and radial basis function (RBF)) in predicting the MFI was evaluated under four scenarios. The average MFI values were between 66.30 ± 15.40 (low erosivity) in Debrecen and 75.39 ± 15.39 (low erosivity) in Pecs. The prediction of the MFI by using MLP was good (NSEBudapest(SC3) = 0.71, NSEPécs(SC2) = 0.69). Additionally, the performance of RBF was accurate (NSEDebrecen(SC4) = 0.68, NSEPécs(SC3) = 0.73). However, the correlation coefficient between the observed MFI and the predicted one ranged between 0.83 (Budapest (SC2-MLP)) and 0.86 (Pécs (SC3-RBF)). Interestingly, the statistical analyses promoted SC2 (Pd-max + pi + Ptotal) and SC4 (Ptotal + Tavg + Td-max + Td-min) as the best scenarios for predicting MFI by using the ANN-MLP and ANN-RBF, respectively. However, the sensitivity analysis highlighted that Ptotal, pi, and Td-min had the highest relative importance in the prediction process. The output of this research promoted the ANN (MLP and RBF) as an effective tool for predicting rainfall erosivity in Central Europe.
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Redes Neurais de Computação , Europa (Continente) , Hungria , TemperaturaRESUMO
Geographic information science (GIS) has emerged as a unique tool that is extremely valuable in various research which involves spatial-temporal aspects. The geographical distribution of the epidemic is considered a significant characteristic that can be analyzed using GIS and spatial statistics. Proper knowledge can assist in controlling, mitigating, and mapping factors for detecting the transmission as well as the disease dynamics, and it provides geographical information of the outbreak and it can also give a glimpse of the disease trend and hotspots as well as provide ways to further evaluate the associated risk. This study analyzed the countries' total confirmed cases, total death cases, and the total recovered cases using an (IDW) geospatial technique which is an inherent tool used in ArcMap for spatial analysis. In order to identify the hotspots for COVID-19 cases, the Getis-Ord Gi* statistic method was applied with a confidence level of 95% in Herat and 90% for Kabul, Kapisa, and Logar provinces. The data considered in this research ranged from the period of 23rd July 2020 to 24th February 2021. All the COVID-19 confirmed, recovered, and death cases were correlated with provincial population density using the Pearson Correlation coefficient. Among the total cases 54,487, 32% cases were reported in the capital of the country (Kabul), and the mortality rate was 31% followed by Herat (18% deaths), Balkh (7% deaths), and Nangarhar (6% deaths). Most of the recoveries were observed in Kabul with (30%) followed by Herat (16%), Bamyan (10%), Balkh (5%), and Kandahar (5%). The results for Global Moran's I showed that the incidence rate of the total COVID-19 cases was in the random pattern, with the Moran Index of - 0.14. Given the z-score of - 1.62, the pattern does not appear to be significantly different than random. There was a strong correlation between the COVID-19 variables and population density [with r(33) = 0.827], [r(33) = 0.819] and [r(33) = 0.817] for the total cases, death cases, and recovered cases, respectively. Even though GIS has limited applicability in detecting the type and its spatial pattern of the epidemic, there is a high potential to use these tools in managing and controlling the pandemic. Moreover, GIS helps us better in comprehending the epidemic and assists us in addressing those fractions of the population and communities which are underserved during the disease outbreak.
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Telomeres protect chromosome ends from degradation. Telomere length (TL) can be altered by aging and environmental stress. Shortened TL has been observed in peripheral blood leukocytes of alcohol dependent subjects and ethanol-exposed somatic cells. To understand the impact of ethanol on telomeres in pluripotent stem cells, we investigated the influence of ethanol on TL and the expression of six Shelterin complex subunit or telomere-regulating genes (POT1, RAP1, TIN2, TPP1, TRF1, and TRF2) in human embryonic stem cells (hESCs), which were exposed to 0, 25, 50, or 100 mM of ethanol for 3, 7, or 14 days. Ethanol-induced TL and Shelterin complex subunit gene expression changes were examined by quantitative polymerase chain reactions. Two-way ANOVA tests indicated that TL variation and expression changes of four associated Shelterin complex subunit genes (POT1, TPP1, TIN2, and TRF2) were mainly dependent on the length of ethanol exposure, while TRF1 and RAP1expression was influenced by ethanol concentration, exposure time, and the interaction of ethanol concentration and exposure time. Tukey's multiple comparison tests showed that TL and the expression of POT1, RAP1, TIN2, TPP1, and TRF1 were decreased after a 7-day (versus a 3-day) ethanol exposure. However, the decreased expression of all six Shelterin complex subunit genes was recovered and TL was not further shortened after a 14-day (versus a 7-day) ethanol exposure, likely due to the adaptation of hESCs to ethanol-induced stress. Our study provided further evidence that TL is regulated and maintained by telomere-regulating genes in stem cells under ethanol stress.
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Células-Tronco Embrionárias Humanas , Telômero , Etanol/toxicidade , Expressão Gênica , Humanos , Complexo Shelterina , Telômero/genética , Proteínas de Ligação a Telômeros/genética , Proteína 2 de Ligação a Repetições Teloméricas/genéticaRESUMO
This study analysed spatio-temporal fluctuations in rainfall to assess drought and wet spells in Khyber Pakhtunkhwa, Pakistan. Temporal changes in rainfall were assessed using a linear regression method, while aridity conditions at each meteorological station were measured using the United Nations Environment Programme climate aridity index. In this study, drought and wet spell patterns were identified using the Standardized Precipitation Evapotranspiration Index (SPEI). The Spearman's Rho (SR) test was applied to find trends in the temporal 1-month and 12-month SPEI data. Balakot, Dir, Kakul, Kalam, Malam Jabba, Parachinar, Patan and Saidu were humid whereas Cherat and Timergara were sub-humid meteorological stations while Bannu, Chitral, Drosh and Peshawar were semi-arid and D.I. Khan was found to be the only arid meteorological station in the study area. The regression results revealed that the amount of rainfall is decreasing at Balakot, Kakul and Dir, while in the southern part of the province the amount of rainfall is increasing, such as in Parachinar and Cherat. The SPEI results revealed distinct drought spells in 1971-1974, 1984-1989, 1998-2004 and recently in 2017-2018, in almost all met-stations results. The SR results indicated a significant wet trend at met-station Parachinar, located in the west, while a significant drying trend has been noted at Balakot in the north-eastern part of the study area. Detailed knowledge about rainfall variability can provide a foundation for the planning and use of water resources.
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Mudança Climática , Secas , Monitoramento Ambiental/métodos , Meteorologia/métodos , Chuva , Análise Espaço-Temporal , Ecossistema , Meteorologia/normas , Paquistão , Estações do Ano , Recursos HídricosRESUMO
A new class of peptides, cyclic cell-penetrating peptides (CPPs), has great potential for delivering a vast variety of therapeutics intracellularly for treating diverse ailments. CPPs have been used previously; however, their further use is limited due to instability, toxicity, endosomal degradation, and insufficient cellular penetration. Cyclic CPPs are being investigated in delivering therapeutics to treat various ailments, including multi-drug resistant microbial infections, HIV, and cancer. They can act as a carrier for a variety of cargos and target intracellularly. Approximately 40 cyclic peptides-based therapeutics are available in the market, and annually one cyclic peptide-based drug enters the market. Numerous research and review articles have been published in the last decade about linear and cyclic peptides separately. This review is the first to provide a comprehensive deliberation about cationic and amphipathic cyclic CPPs. Herein, we highlights their structures, significant advantages, translocation mechanisms, and delivery application in the area of biomedical sciences.
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Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/farmacocinética , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Penetradores de Células/química , Endossomos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/classificaçãoRESUMO
Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0-143.5) months, significantly longer compared to 93.7 (95% CI, 60.3-127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer.
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Proteínas Morfogenéticas Ósseas/fisiologia , Neoplasias da Mama/patologia , Animais , Proteínas Morfogenéticas Ósseas/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Metástase Linfática , Camundongos , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/análise , Receptores de Estrogênio/análiseRESUMO
The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.
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Currently, a global pandemic era of public health concerns is going on with the Coronavirus Disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of COVID-19 was reported from Wuhan's Huanan seafood market in China late December 2019. Bats, pangolins, and snakes have been nominated as salient carriers of the virus. Thanks to its high pathogenicity, it can cause severe respiratory infections. Fever, dry cough, sore throat, pneumonia, septic shock, and ground-glass opacities are the foremost clinical manifestations of COVID-19. Immunocompromised patients are at high risk for COVID-19 infection and may lead to death. Scientist and government agencies around the globe are putting forward their best efforts and resources for the effective treatment of human coronavirus infections; however, neither vaccines nor antiviral drugs are available for the treatment of human coronaviruses (HCoV) infections such as SARS (severe acute respiratory syndrome), MERS (Middle Eastern respiratory syndrome), and COVID-19. Since the outbreak, a plethora of research and review articles have been published. Moreover, the mass media has bombarded the public with conflicting opinions about the pandemic. There is a dire need for accurate and reliable information concerning this pandemic. In this review, we have compiled the up to date information about the origins, evolution, epidemiology, and pathogenesis of this disease. Moreover, very few reports have addressed the clinical features and current status of treatment for COVID-19; we have adequately addressed these topics in detail in this review. Finally, a detailed account of clinical trials of vaccines and other therapeutics currently in progress has been delineated.
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Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Humanos , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , SARS-CoV-2 , Vacinas Virais/uso terapêuticoRESUMO
Chromatographic analysis of the alcoholic extract from Salsola imbricata yielded two new secondary metabolites, salisomide (1) and salisoflavan (2). Their structures were established with the help of spectroscopic techniques including COSY, HMQC and HMBC NMR experiments.
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Amidas/química , Flavonoides/química , Fenóis/química , Salsola/química , Amidas/metabolismo , Flavonoides/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Fenóis/metabolismo , Salsola/metabolismoRESUMO
OBJECTIVE: To evaluate the role of surgical ligation of scrotal varicocele for treatment of male factor infertility. METHODS: We studied 60 patients who presented with infertility and were also found to have scrotal varicocele. Patients with other probable causes contributing to infertility were excluded. Diagnosis was made by clinical examination and scrotal ultrasonography. All the patients underwent either laparoscopic varicocelectomy or open retroperitoneal high ligation of the testicular veins. Operative time and hospital stay was recorded. All patients were evaluated for postoperative improvement of semen parameters and development of any postoperative complication. The results were analyzed by commercially available software. RESULTS: During the study period 5 patients were lost to follow up and were excluded. The rest of patients (n=55) were young, with age ranging from 20-35 years (Mean age 27.8 years, SD +/- 4.38). All patients had unilateral left sided varicocele; two patients (3.6%) had grade I varicocele, 21 patients (38.2%) had grade II varicocele and 32 patients (58.2%) had grade III varicocele. Statistically significant improvement in sperm density (p value < 0.05), sperm activity (p value < 0.05) and sperm morphology (p value < 0.05) was observed after the surgical ligation. The mean operative time was 54.88 minutes (SD + 13). The mean hospital stay in laparoscopic procedure was 33.4 (SD + 15.3). Minor complications were noted in 13 patients and included superficial wound infection in 3 patients, 6 patients exhibited testicular pain and persistence of varicocele in 4 patients. CONCLUSION: Surgical ligation of scrotal varicocele is asafe and effective mode of treatment of male factor infertility in selected population.
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Infertilidade Masculina/cirurgia , Escroto/cirurgia , Varicocele/cirurgia , Adulto , Estudos Transversais , Humanos , Ligadura/métodos , MasculinoRESUMO
The sorption efficiency of chickpea husk of black gram variety (BGH), for the removal of organophosphorous pesticides (OPPs), i.e. triazophos (TAP) and methyl parathion (MP) from aqueous media has been investigated. Optimization of operating sorption parameters, i.e. particle size, sorbent dose, agitation time, pH, initial concentration of sorbates, and temperature has been studied. The sorption data fitted well to Freundlich, Langmuir and Dubinin-Radushkevich (D-R) sorption isotherms. The maximum sorption capacities of BGH for TAP and MP were calculated to be 3.5+/-0.45 and 10.6+/-0.83 mmol g(-1) by Freundlich, 0.0077+/-0.021 and 0.025+/-0.0094 mmol g(-1) by Langmuir and 0.48+/-0.037 and 0.15+/-0.077 mmol g(-1) by D-R isotherms respectively, employing 0.2g of sorbent, at pH 6, 90 min agitation time and at 303 K. Application of first order Lagergren and Morris-Weber equations to the kinetic data yielded correlation coefficients, close to unity and showed partial intra-particle diffusion. The negative values of thermodynamic parameters, i.e. DeltaH (kJ mol(-1)), DeltaS (J mol(-1) K(-1)) and DeltaG (kJ mol(-1)) indicate the exothermic and spontaneous nature of the sorption process. The sorbed pesticides were recovered by sonication with methanol, making the regeneration and reutilization of the sorbents promising. The investigated sorbent exhibited potential applications in water decontamination, treatments of industrial and agricultural waste waters and thus productively demonstrated viable use of agricultural waste material.