Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Genomic characterization of Puccinia triticina using molecular marker technology / Caracterização genômica de Puccinia triticina usando tecnologia de marcadores moleculares

Leaf rust, caused by Puccinia triticina, is the most common rust disease of wheat. The fungus is an obligate parasite capable of producing infectious urediniospores. To study the genetic structure of the leaf rust population 20 RAPD primers were evaluated on 15 isolates samples collected in Pakistan. A total of 105 RAPD fragments were amplified with an average of 7 fragments per primer. The number of amplified fragments varied from 1 to 12. GL Decamer L-07 and GL Decamer L-01 amplified the highest number of bands (twelve) and primer GL Decamer A-03 amplified the lowest number of bands i.e one. Results showed that almost all investigated isolates were genetically different that confirms high genetic diversity within the leaf rust population. Rust spores can follow the migration pattern in short and long distances to neighbor areas. Results indicated that the greatest variability was revealed by 74.9% of genetic differentiation within leaf rust populations. These results suggested that each population was not completely identical and high gene flow has occurred among the leaf rust population of different areas. The highest differentiation and genetic distance among the Pakistani leaf rust populations were detected between the leaf rust population in NARC isolate (NARC-4) and AARI-11and the highest similarity was observed between NARC isolates (NARC-4) and (NARC-5). The present study showed the leaf rust population in Pakistan is highly dynamic and variable.

A ferrugem da folha, causada por Puccinia triticina, é a ferrugem mais comum do trigo. O fungo é um parasita obrigatório, capaz de produzir urediniósporos infecciosos. Para estudar a estrutura genética da população de ferrugem da folha, 20 primers RAPD foram avaliados em 15 amostras de isolados coletadas no Paquistão. Um total de 105 fragmentos RAPD foram amplificados com uma média de 7 fragmentos por primer. O número de fragmentos amplificados variou de 1 a 12. GL Decamer L-07 e GL Decamer L-01 amplificaram o maior número de bandas (doze), e o primer GL Decamer A-03 amplificou o menor número de bandas, ou seja, um. Os resultados mostraram que quase todos os isolados investigados eram geneticamente diferentes, o que confirma a alta diversidade genética na população de ferrugem da folha. Os esporos de ferrugem podem seguir o padrão de migração em distâncias curtas e longas para áreas vizinhas. Os resultados indicaram que a maior variabilidade foi revelada por 74,9% da diferenciação genética nas populações de ferrugem. Esses resultados sugeriram que cada população não era completamente idêntica e um alto fluxo gênico ocorreu entre a população de ferrugem da folha de diferentes áreas. A maior diferenciação e distância genética entre as populações de ferrugem da folha do Paquistão foram detectadas entre a população de ferrugem da folha no isolado NARC (NARC-4) e AARI-11 e a maior similaridade foi observada entre os isolados NARC (NARC-4) e (NARC-5). O presente estudo mostrou que a população de ferrugem da folha no Paquistão é altamente dinâmica e variável.

Effects of ileocolonic delivered vitamin B2, B3 and C (ColoVit) or the Groningen anti-inflammatory diet on disease course and microbiome of patients with Crohn's disease (VITA-GrAID study): a protocol for a randomised and partially blinded trial.

BACKGROUND: Diet plays a pivotal role in the onset and progression of Crohn's disease (CD). Nutritional interventions revealed effects on intestinal inflammation and gut microbial composition. However, data from well-designed and controlled dietary trials are lacking. Therefore, evidence-based dietary recommendations are still unavailable to patients and physicians. Here, we aim to investigate the effects of an evidence-based anti-inflammatory diet, and an ileocolonic-targeted capsule containing vitamin B2, B3 and C (ColoVit) on patients with CD and their healthy household members. METHODS AND ANALYSIS: In this multicentre, randomised, placebo-controlled, partially blinded nutritional intervention trial, we aim to recruit 255 CD patients with Harvey-Bradshaw Index <8 and a faecal calprotectin (FCal) cut-off of ≥100 µg/g at baseline. Participants will be randomised into two experimental intervention groups and one placebo group. In the experimental groups, participants will either adhere to the Groningen anti-inflammatory diet (GrAID) or ingest an ileocolonic-delivered oral vitamin B2/B3/C capsule (ColoVit). The study consists of a 12-week controlled interventional phase, which proceeds to a 9-month observational follow-up phase in which patients allocated to the GrAID group will be requested to continue the intervention on their own accord. Household members of participating patients will be asked to participate in the trial as healthy subjects and are allocated to the same group as their peer. The primary study outcome for patients is the change in FCal level from baseline. The primary outcome for household members is the change in gut microbial composition, which is set as secondary outcome for patients. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board of the Stichting Beoordeling Ethiek Biomedisch Onderzoek in Assen, the Netherlands. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04913467.

Population distribution and habitat analysis of Rufous treepie (Dendrocitta vagabunda) in Abbottabad, Pakistan / Distribuição da população e análise de habitat de Rufous treepie (Dendrocitta vagabunda) em Abbottabad, Paquistão

Abstract The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). "The ''Point count Method" was used for population estimation and ''Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.

Resumo A trepadeira Rufous (Dendrocitta vagabunda) pertence à família corvidae, ordem Passeriformes que inclui cerca de 100 espécies. O estudo atual foi realizado para reunir informações sobre a distribuição da população e análise do habitat de D. vagabunda no distrito de Abbottabad, Paquistão. Os dados foram coletados mensalmente pela manhã e à noite (2018-2019). O "método de contagem de pontos" foi usado para estimativa da população e o "método dos quadrados" para análise de habitat da área de estudo. O resultado mostra que uma densidade populacional média mensal de D. vagabunda foi máxima em Jhangra 0,14 ± 0,039 / ha, enquanto a mínima em Havelian 0,11 ± 0,022/ha. Não houve diferença significativa (p> 0,05) entre as densidades populacionais mensais de D. vagabunda, entretanto foi encontrada diferença significativa (p <0,05) entre os períodos matutino e noturno da população da espécie. O presente estudo revelou que o índice de valor de importância (IVI) das espécies de plantas em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 59,6 ± 12,6, 50,1 ± 6,9, 53,4 ± 6,3, 66,8 ± 10 e 60,1 ± 7,7. Da mesma forma, a frequência de arbustos em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 33,3 ± 4,2, 45 ± 9,4, 46,7 ± 8,2, 55,6 ± 22,2 e 37,5 ± 8,5. Da mesma forma, a frequência de ervas em Sherwan, Bakot, Havelian, Langra e Jhangra foi: 40,4 ± 6,0, 37,5 ± 5,6, 53,3 ± 7,4, 48,5 ± 5,2 e 46,9 ± 7,4, respectivamente. Nossos resultados mostram a área de estudo como habitat adequado para D. vagabunda.

Antioxidant potential and α-glucosidase inhibitory activity of onion (Allium cepa L. ) peel and bulb extracts / Atividade antioxidante e potencial inibidor de glucosidase de extratos de casca e bulbo de cebola (Allium cepa) preparados por etanol e água

Abstract Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2'-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared to the inner bulb. The information obtained by the present study can be useful in promoting the use of vegetable parts other than the edible mesocarp for several future food applications, rather than these being wasted.

Resumo Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2'-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades antioxidantes, em comparação com o bulbo interno. As informações obtidas pelo presente estudo podem promover o uso de outras partes vegetais além do mesocarpo comestível para futuras aplicações em alimentos, ao invés de serem desperdiçadas.

Antioxidant potential and alfa-glucosidase inhibitory activity of onion (Allium cepa L. ) peel and bulb extracts / Atividade antioxidante e potencial inibidor de alfa-glucosidase de extratos de casca e bulbo de cebola (Allium cepa) preparados por etanol e água

Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared [...].(AU)

Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades [...].(AU

Population distribution and habitat analysis of Rufous treepie (Dendrocitta vagabunda) in Abbottabad, Pakistan / Distribuição da população e análise de habitat de Rufous treepie (Dendrocitta vagabunda) em Abbottabad, Paquistão

The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). The "Point count Method" was used for population estimation and "Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.(AU)

A trepadeira Rufous (Dendrocitta vagabunda) pertence à família corvidae, ordem Passeriformes que inclui cerca de 100 espécies. O estudo atual foi realizado para reunir informações sobre a distribuição da população e análise do habitat de D. vagabunda no distrito de Abbottabad, Paquistão. Os dados foram coletados mensalmente pela manhã e à noite (2018-2019). O "método de contagem de pontos" foi usado para estimativa da população e o "método dos quadrados" para análise de habitat da área de estudo. O resultado mostra que uma densidade populacional média mensal de D. vagabunda foi máxima em Jhangra 0,14 ± 0,039 / ha, enquanto a mínima em Havelian 0,11 ± 0,022/ha. Não houve diferença significativa (p> 0,05) entre as densidades populacionais mensais de D. vagabunda, entretanto foi encontrada diferença significativa (p <0,05) entre os períodos matutino e noturno da população da espécie. O presente estudo revelou que o índice de valor de importância (IVI) das espécies de plantas em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 59,6 ± 12,6, 50,1 ± 6,9, 53,4 ± 6,3, 66,8 ± 10 e 60,1 ± 7,7. Da mesma forma, a frequência de arbustos em Sherwan, Bakot, Havelian, Langra e Jhangra foi de: 33,3 ± 4,2, 45 ± 9,4, 46,7 ± 8,2, 55,6 ± 22,2 e 37,5 ± 8,5. Da mesma forma, a frequência de ervas em Sherwan, Bakot, Havelian, Langra e Jhangra foi: 40,4 ± 6,0, 37,5 ± 5,6, 53,3 ± 7,4, 48,5 ± 5,2 e 46,9 ± 7,4, respectivamente. Nossos resultados mostram a área de estudo como habitat adequado para D. vagabunda.(AU)

Community- vs. hospital-based management of multidrug-resistant TB in Pakistan.

BACKGROUND Multidrug-resistant TB (MDR-TB) treatment takes 18-24 months and is complex, costly and isolating. We provide trial evidence on the WHO Pakistan recommendation for community-based care rather than hospital-based care.METHODS Two-arm, parallel-group, superiority trial was conducted in three programmatic management of drug-resistant TB hospitals in Punjab and Sindh Provinces, Pakistan. We enrolled 425 patients with MDR-TB aged >15 years through block randomisation in community-based care (1-week hospitalisation) or hospital-based care (2 months hospitalisation). Primary outcome was treatment success.RESULTS Among 425 patients with MDR-TB, 217 were allocated to community-based care and 208 to hospital-based care. Baseline characteristics were similar between the community and hospitalised arms, as well as in selected sites. Treatment success was 74.2% (161/217) under community-based care and 67.8% (141/208) under hospital-based care, giving a covariate-adjusted risk difference (community vs. hospital model) of 0.06 (95% CI -0.02 to 0.15; P = 0.144).CONCLUSIONS We found no clear evidence that community-based care was more or less effective than hospital-based care model. Given the other substantial advantages of community-based care over hospital based (e.g., more patient-friendly and accessible, with lower treatment costs), this supports the adoption of the community-based care model, as recommended by the WHO.

Molecular detection and therapeutic study of Trypanosoma brucei evansi from naturally infected horses in Punjab, Pakistan.

Trypanosomiasis is one of the severe pathogenic infections, caused by several Trypanosoma species, affecting both animals and humans, causing substantial economic losses and severe illness. The objective of this study was to determine the molecular diagnosis and the risk factors associated with trypanosomiasis in District Jhang, Punjab, Pakistan. For this purpose, blood samples were randomly collected from 200 horses. A predesigned questionnaire was used to collect data on risk factors before the sample collection. The microscopy examination through Giemsa staining, formol gel test and PCR techniques were used to find the prevalence. The prevalence was recorded as 22.5% with microscopy examination, 21% through formol gel test and 15.5% with PCR based results. Analysis of risk factors associated with Trypanosoma brucei evansi occurrence was carried out using Chi-square test. It showed the prevalence of Trypanosoma brucei evansi was significantly (p⟨0.05) associated with sex, age, rearing purpose and body condition whereas non-significantly (p⟩0.05) with insects control practices. This study supports the idea that PCR is a sensitive, robust and more reliable technique to diagnose trypanosomiasis. It was concluded that Trypanosoma brucei evansi is widely prevalent in Jhang (Pakistan), highlighting a dire need to develop control strategies and education programmes to control this disease in developing countries.

Genomic characterization of Puccinia triticina using molecular marker technology.

Leaf rust, caused by Puccinia triticina, is the most common rust disease of wheat. The fungus is an obligate parasite capable of producing infectious urediniospores. To study the genetic structure of the leaf rust population 20 RAPD primers were evaluated on 15 isolates samples collected in Pakistan. A total of 105 RAPD fragments were amplified with an average of 7 fragments per primer. The number of amplified fragments varied from 1 to 12. GL Decamer L-07 and GL Decamer L-01 amplified the highest number of bands (twelve) and primer GL Decamer A-03 amplified the lowest number of bands i.e one. Results showed that almost all investigated isolates were genetically different that confirms high genetic diversity within the leaf rust population. Rust spores can follow the migration pattern in short and long distances to neighbor areas. Results indicated that the greatest variability was revealed by 74.9% of genetic differentiation within leaf rust populations. These results suggested that each population was not completely identical and high gene flow has occurred among the leaf rust population of different areas. The highest differentiation and genetic distance among the Pakistani leaf rust populations were detected between the leaf rust population in NARC isolate (NARC-4) and AARI-11and the highest similarity was observed between NARC isolates (NARC-4) and (NARC-5). The present study showed the leaf rust population in Pakistan is highly dynamic and variable.

Protection and controlled release of vitamin C by different micro/nanocarriers.

Ascorbic acid, known as vitamin C, is an important antioxidant and food ingredient, and highly sensitive to environmental conditions, which makes its incorporation into food, cosmetic and pharmaceutical products more difficult. The evaluation of its nano/microencapsulation enables the improvement of its stability and controlled release. There are various investigations regarding ascorbic acid encapsulation; however, a deep study related to the scale-up of encapsulation process, its application into food products and digestibility study are still needed. This review highlights the main physicochemical and health properties of vitamin C, recent advances of its encapsulation into micro/nanocarriers, and application in food products. Also, the controlled release and bioavailability of encapsulated forms within different carriers is underlined. The results of published studies clearly show that vitamin C can be successfully protected within micro/nanoencapsulation systems and it can be applied as an efficient ingredient in the formulation of various food products such as bakery goods.

Influence of Phytase with Or without Organic Acid (Sodium Di-Formate) Supplementation on Growth Performance, Carcass Response, Protein and Mineral Digestibility in Starter Phase of Broilers

This experiment was planned to evaluate the effects of phytase supplementation with or without organic acid (OA) on performance, protein, calcium (Ca), phosphorus (P) and sodium (Na) digestibility and carcass parameters in broiler chickens fed low Ca and low P diets in comparison to a high Ca and high P diet with standard specifications. For this purpose, two iso-nitrogenous and iso-caloric diets were prepared in such a way that one diet had high Ca (9.80) and high P (4.50) and second diet had low Ca (8.50) and low P (2.40), respectively. Low Ca and low P diet was further supplemented with enzyme phytase @ 500 FTU/kg, and phytase @ 500 FTU/kg + organic acid (1 kg/ton). Rations were offered to seven replicates of ten birds each, from day 1 to 21. Results revealed that the experimental treatments had no effect on feed intake and growth performance of birds (p>0.05). Carcass parameter results showed highest thigh meat yield % and liver weight % in the birds fed diet with low Ca & P and supplemented with enzymes phytase (p<0.05). Fecal P and Na digestiblities were high (p<0.05) in experimental broilers fed low Ca low P with enzyme phytase supplementation as compared to the diet without phytase supplementation. It is concluded that phytase and OA supplementation in the starter diet with low Ca and low P level did not influence intake, growth and feed conversion of the broilers. However, thigh meat yield percent and mineral digestiblities (P and Na) increased in the broilers that received the diet with low Ca and low P level and supplemented with enzyme phytase.(AU)

Efficacy of Tulsi (Ocimum Sanctum) Plant Powder on Health, Growth and Carcass Traits of Japanese Quail (Coturnix Japonica)

The objective of the current work was to assess the effects of Tulsi plant powder on the health, growth and carcass characteristics of Japanese quail. In total, 300 quails (1-week old) were distributed into four treatment groups with five replicates each. The first group (T0) was a control group where a basal standard diet was offered to the birds. Groups T0.5, T1 and T1.5 were supplemented with Tulsi plant powder at a rate of 0.5%, 1%, 1.5%, respectively. Data were analyzed in SPSS software by applying one-way ANOVA and significant and notable means were analyzed through Duncan's New Multiple Range Test. Dietary supplementation of T1.5 significantly (p≤0.05) increased the feed intake, body weight, gain in weight and presented a better feed conversion ratio. Significantly higher glucose, total cholesterol, HDL, WBCs, RBCs and HCT were observed in the quails from T1 than in the control group (p≤0.05). However, the quails from T1.5 had significantly (p≤0.05) higher hemoglobin, MCV, platelets and total protein contents. On the other hand, the T0 group was only higher in LDL contents. Non-significant (p>0.05) in MCH, MCHC, triglyceride, VLDL were noted among the experimental groups. It was concluded that the dietary supplementation of Tulsi plant powder at 1.5 % is beneficial for improving the growth performance and can be used in the diet of Japanese quail without compromising the health status and carcass traits.(AU)

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.

Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Antioxidant potential and α-glucosidase inhibitory activity of onion (Allium cepa L.) peel and bulb extracts.

Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2'-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared to the inner bulb. The information obtained by the present study can be useful in promoting the use of vegetable parts other than the edible mesocarp for several future food applications, rather than these being wasted.

Population distribution and habitat analysis of Rufous treepie (Dendrocitta vagabunda) in Abbottabad, Pakistan.

The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). "The ''Point count Method" was used for population estimation and ''Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.

Phageome-based vaccination and human innate immune modulation could be a useful strategy to control human Coronavirus infections.

Human Coronavirus (CoV) infections, including SARS-COV, MERS-COV, and SARS-CoV-2, usually cause fatal lower and upper respiratory tract infections due to exacerbated expression of pro-inflammatory cytokines and chemokines. We aim to summarize different aspects, such as CoV immune evasion mechanisms and host innate immune response to these infections, and their role in pathogenesis. We have also elaborated the up-to-date findings on different vaccine development strategies and progress against CoVs in both humans and non-human models. Most importantly, we have described the Phageome-human immune interaction, its therapeutic usage as anti-viral, anti-inflammatory agent, and implications for multiple vaccine development systems. The data suggest that endogenous phages might play a vital role in eliminating the infection and regulating the body's immune system. Considering the innate-immune-induced pathogenesis against CoVs and the therapeutic aptitude of phageome, we propose that the prophylactic administration of phages and phage-based vaccines could be a useful strategy to control the emerging CoV infections.

In silico analysis of Naegleria fowleri cathepsin B paralogs: important drug targets.

Naegleria fowleri is a deadly human pathogen that causes primary amoebic meningoencephalitis (PAM). In this study, in silico investigations of two important N. fowleri cathepsin B paralogs, i.e., copies of genes resulting from a gene duplication event, were carried out using comparative modeling and molecular dynamics (MD) simulations. Comparative models of both paralogs showed significant architectural similarity with their template, i.e., rat cathepsin B. However, in N. fowleri cathepsin B (UniProt ID: X5D761) and putative cathepsin B (UniProt ID: M1HE19) enzymes, eleven and fifteen residues in the occluding loop regions were deleted, respectively, suggesting that these enzymes have a short occluding loop. Thus, it is concluded that N. fowleri cathepsin B and putative cathepsin B enzymes lack exopeptidase activity but possess enhanced endopeptidase activity and an affinity for macromolecular inhibitors. MD simulations further confirmed that prosegments (macromolecular inhibitors) bond more tightly with both enzymes than with wild-type cathepsin B. Additionally, a mutation was identified at an important N-glycosylation site; this mutation is believed to affect cathepsin B targeting inside the cell and make cathepsin B available in the extracellular environment. Due to this important N-glycosylation site mutation, these enzymes are secreted in the extracellular environment via an alternative, still unknown, posttranslational processing strategy. The present study is the first to predict the three-dimensional folds of N. fowleri cathepsin B paralogous enzymes, including a detailed description of the active site architecture and information about propeptide binding mode. This information can contribute to the discovery of novel and selective treatments that are effective against N. fowleri.

In vivo assessment of bisphenol A induced histopathological alterations and inflammatory gene expression in lungs of male Wistar rats.

Bisphenol A (BPA), an imperative environmental contaminant used in polycarbonate plastics. Due to limited information concerning the effect of BPA on lungs, this study design to assess whether BPA cause alterations in histopathology and trace metal content in lungs of rats. They were divided into five groups with five rats per group. Group I was named as control group. Group L6 and L12 were received BPA (10 mg/kg body weight/day) for 6 weeks and 12 weeks respectively. Group H6 and L12 were given BPA (25 mg/kg body weight/day) for 6 weeks and 12 weeks respectively. Considerable alteration in Cu, Zn and Fe was detected in experimental groups. BPA also caused significant increase in the expression of tumor necrosis factor α that mediate the pulmonary inflammatory response. Comparative study of resolved proteins i.e. 72 KDa (matrix metalloproteinase 2 fragment) and 109 KDa (nucleolin) on SDS-PAGE showed their altered expression in experimental groups. Histopathology of experimental groups revealed altered architecture of lungs. Special staining of BPA treated groups showed significant number of mast cells in alveoli and bronchioles. Prolonged administration of BPA causes deleterious aggravating lung damage even at extremely low dose, so the use of BPA should be prohibited in plastic synthesizing industries.