Progressive familial intrahepatic cholestasis-outcome and time to transplant after biliary diversion according to genetic subtypes.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous disease characterized by progressive cholestasis in early childhood. Surgical therapy aims at preventing bile absorption either by external or internal biliary diversion (BD). Several different genetic subtypes encode for defects in bile transport proteins, and new subtypes are being discovered ongoingly. Overall, the literature is scarce, however, accumulating evidence points to PFIC 2 having a more aggressive course and to respond less favorable to BD. With this knowledge, we aimed to retrospectively analyze the long-term outcome of PFIC 2 compared to PFIC 1 following BD in children at our center. Methods: Clinical data and laboratory findings of all children with PFIC, who were treated and managed in our hospital between 1993 and 2022, were analyzed retrospectively. Results: Overall, we treated 40 children with PFIC 1 (n = 10), PFIC 2 (n = 20) and PFIC 3 (n = 10). Biliary diversion was performed in 13 children (PFIC 1, n = 6 and 2, n = 7). Following BD, bile acids (BA) (p = 0.0002), cholesterol (p < 0.0001) and triglyceride (p < 0.0001) levels significantly decreased only in children with PFIC 1 but not in PFIC 2. Three out of 6 children (50%) with PFIC 1 and 4 out of 7 children (57%) with PFIC 2 required liver transplantation despite undergoing BD. On an individual case basis, BA reduction following BD predicted this outcome. Of the 10 children who had PFIC 3, none had biliary diversion and 7 (70%) required liver transplantation. Conclusion: In our cohort, biliary diversion was effective in decreasing bile acids, cholesterol levels as well as triglycerides in the serum only in children with PFIC 1 but not PFIC 2. On an individual case level, a decrease in BA following BD predicted the need for liver transplantation.

Post-bleaching alterations in coral reef communities.

We explored the extent of post-bleaching impacts, caused by the 2014-2016 El Niño Southern Oscillation (ENSO) event, on benthic community structure (BCS) and herbivores (fish and sea urchins) on seven fringing reefs, with differing protection levels, in Zanzibar, Tanzania. Results showed post-bleaching alterations in BCS, with up to 68 % coral mortality and up to 48 % increase in turf algae cover in all reef sites. Herbivorous fish biomass increased after bleaching and was correlated with turf algae increase in some reefs, while the opposite was found for sea urchin densities, with significant declines and complete absence. The severity of the impact varied across individual reefs, with larger impact on the protected reefs, compared to the unprotected reefs. Our study provides a highly relevant reference point to guide future research and contributes to our understanding of post-bleaching impacts, trends, and evaluation of coral reef health and resilience in the region.

Xanthones: A Class of Heterocyclic Compounds with Anticancer Potential.

Xanthones (9H xanthen-9-one) are an important class of heterocyclic compounds containing oxygen and a moiety of gamma-pirone, dense with a two-benzene ring structure, distributed widely in nature. Naturally occurring xanthones are found in micro-organisms and higher plants as secondary metabolites in fungi and lichens. Compounds of the family Caryophyllaceae, Guttiferae and Gentianaceae, are the most common natural source of xanthones. The structure of the xanthones nucleus, coupled with its biogenetic source, imposes that the carbons are numbered according to the biosynthetic pact. The characteristics oxygenation pattern of xanthones earlier is mixed shikimateacetate biogenesis. The major class of xanthones includes simple oxygenated, non-oxygenated, xanthonolignoids, bisxanthones, prenylated and related xanthones, miscellaneous xanthones. Their great pharmacological importance and interesting scaffolds were highly encouraged by scientists to investigate either the synthesis design or natural products for cancer treatment. Because currently used antitumor drugs possess high toxicity and low selectivity, efficacious treatment may be compromised. This review is limited to the antitumor activity of xanthones and the chemistry of xanthone core, which may help provide fundamental knowledge to the medicinal chemist for new and advanced research in drug development.

Nanoparticles in clinical trials of COVID-19: An update.

Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.

Depth and habitat are important drivers of abundance for predatory reef fish off Pemba Island, Tanzania.

Coral reefs across the world face significant threats from fishing and climate change, which tends to be most acute in shallower waters. This is the case off Pemba Island, Tanzania, yet the effects of these anthropogenic stressors on the distribution and abundance of economically and ecologically important predatory reef fish, including how they vary with depth and habitat type, is poorly understood. Thus, we deployed 79 baited remote underwater videos (BRUVs) in variable water depths and habitats off Pemba Island, and modeled the effects of depth and habitat on abundance of predatory reef fish. Predatory reef fish types/taxa were significantly predicted by depth and habitat types. Habitats in relatively deeper waters and dominated by hard and soft corals hosted high species richness and abundance of predatory reef fish types/taxa compared to mixed sandy and rubble habitats. The findings add to the growing evidence that deep waters around coral reefs are important habitats for predatory reef fish. Thus, careful management, through effective area and species protection measures, is needed to prevent further depletion of predatory reef-associated fish populations and to conserve this biologically important area.

METALLOTHIONEIN-2A (RS1610216&RS28366003) GENE POLYMORPHISMS AND THE RISK OF STOMACH ADENOCARCINOMA.

BACKGROUND: Gastric cancer is the fourth most common cause of worldwide cancer. Also in contrast to the huge advances in curing, the chance of living is very low even in surgery cases. Having a genetic predisposition plays an important role in cancer development. The association between Metallothionein-2A gene polymorphisms and the risk of adenocarcinoma has been widely studied, yet there is only one study on stomach diseases. OBJECTIVE: In this study, we aimed to investigate the association between 2 (MT-2A) polymorphisms and adenocarcinoma. METHODS: This cross-sectional case control study was performed between Mach 2014 and January 2015 at the Tuba Hospital of Sari, Iran. Peripheral blood samples were collected in EDTA tube. DNA extraction was performed using the spin column procedure. The MT-2A polymorphisms MT-2A (rs1610216), (rs28366003) were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 95 a topic adenocarcinoma patients and 90 healthy individuals from Iranian population. RESULTS: The MT-2A rs1610216 polymorphism increased the risk of adeno carcinoma in our Iranian population [OR: 3.8533; 95%CI, 1.3155-11.2869; P=0.0139] and rs28366003 [OR: 4.0978; 95%CI, 1.2521-13.4108; P=0.0197]. CONCLUSION: The MT-2A gene polymorphism was associated with the risk of adenocarcinoma in the Iranian population.

Metallothionein-2a (rs1610216&rs28366003) gene polymorphisms and the risk of stomach adenocarcinoma / Polimorfismos do gene metalotioneína-2A (rs1610216& rs28366003) e o risco de adenocarcinoma de estômago

ABSTRACT BACKGROUND: Gastric cancer is the fourth most common cause of worldwide cancer. Also in contrast to the huge advances in curing, the chance of living is very low even in surgery cases. Having a genetic predisposition plays an important role in cancer development. The association between Metallothionein-2A gene polymorphisms and the risk of adenocarcinoma has been widely studied, yet there is only one study on stomach diseases. OBJECTIVE: In this study, we aimed to investigate the association between 2 (MT-2A) polymorphisms and adenocarcinoma. METHODS: This cross-sectional case control study was performed between Mach 2014 and January 2015 at the Tuba Hospital of Sari, Iran. Peripheral blood samples were collected in EDTA tube. DNA extraction was performed using the spin column procedure. The MT-2A polymorphisms MT-2A (rs1610216), (rs28366003) were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 95 a topic adenocarcinoma patients and 90 healthy individuals from Iranian population. RESULTS: The MT-2A rs1610216 polymorphism increased the risk of adeno carcinoma in our Iranian population [OR: 3.8533; 95%CI, 1.3155-11.2869; P=0.0139] and rs28366003 [OR: 4.0978; 95%CI, 1.2521-13.4108; P=0.0197]. CONCLUSION: The MT-2A gene polymorphism was associated with the risk of adenocarcinoma in the Iranian population.

RESUMO CONTEXTO: O câncer gástrico é a quarta causa mais comum de câncer em todo o mundo. Também em contraste com os enormes avanços na cura, a chance de viver é muito baixa, mesmo em casos de cirurgia. Ter uma predisposição genética desempenha um papel importante no desenvolvimento do câncer. A associação entre polimorfismos do gene metalotioneína-2A e o risco de adenocarcinoma tem sido amplamente estudada, mas há apenas um estudo sobre doenças estomacais. OBJETIVO: Neste estudo, objetivou-se investigar a associação entre 2 (MT-2A) polimorfismos e adenocarcinoma. MÉTODOS: Um estudo de controle de caso transversal foi realizado entre março de 2014 e janeiro de 2015 no hospital Tuba, Sari, Irã. Amostras de sangue periférico foram coletadas em tubo EDTA. A extração do ADN foi executada usando o procedimento da coluna da rotação. Os polimorfismos MT-2a MT-2A (rs1610216), (rs28366003) foram determinados pela análise do polimorfismo do comprimento do fragmento da reação-limitação de cadeia da polimerase em 95 pacientes com adenocarcinoma tópico e em 90 indivíduos saudáveis da população iraniana. RESULTADOS: O polimorfismo MT-2A rs1610216 aumentou o risco de adenocarcinoma de em nossa população iraniana. [OR: 3,8533; 95%CI, 1,3155-11,2869; P=0,0139] e rs28366003 [OR: 4,0978; 95%CI, 1,2521-13,4108; P=0,0197]. CONCLUSÃO: O polimorfismo do gene MT-2A foi associado ao risco de adenocarcinoma na população iraniana.

Protective Role of Carissa edulis Ethanolic Extract Against Dimethoate-induced Hepatotoxicity in Guinea Pigs.

BACKGROUND AND OBJECTIVE: Carissa edulis (CE) (Apocynaceae) is distributed in tropical Africa and Asia and commonly used in folk medicine to treat many diseases such as headache, cough, rheumatism and fever. The purpose of this study was to evaluate the protective role of ethanolic extract of CE, a medicinal plant locally called "Al-Arm" in Yemen, against liver injury induced by dimethoate (DM) intoxication in male guinea pigs. MATERIALS AND METHODS: Animals were divided randomly into 5 groups and kept at 5 animals per group. The first group was served as a control group and administered with vehicle orally; the group II administered with DM (14 mg kg-1; 1/25 LD50) orally. Animals of group III, IV and V were administered with 100 mg kg-1 of CE extract, 200 mg kg-1 of CE extract and 100 mg kg-1 Liv-52 orally half hour before DM administration, respectively. All the previous administrations were repeated daily for 21 days. Data were analyzed by one-way ANOVA using SPSS. RESULTS: The DM caused a statistically significant increase in the serum level of liver enzymes (AST, ALT, ALP) when compared to control animals, whereas CE and Liv-52 pre-treatment to the DM-intoxicated animals resulted in a significant normalization of the activities of enzymes. Similarly, a significant increase in lipid peroxidation (LPO) level, while induced significant decreases in the activities of liver catalase (CAT) and glutathione-S-transferase (GST). In contrast, co-administration of CE and Liv-52 to DM-treated animals restored most of these biochemical parameters to nearly normal levels. Histopathological examination of intoxicated animals showed many tissues alterations such as; vasodilation, hemorrhage, cytoplasmic vacuolization, inflammation and nuclear pyknosis indicating liver damage, while the animals received CE or Liv-52 showed less pathological effects when compared to animals treated with DM alone. CONCLUSION: The biochemical and histological results confirmed the hepatoprotective effect of ethanolic extract of CE against DM-induced hepatotoxicity in male guinea pigs.

Níveis séricos de citocinas IL-2, IL-10 e IL-12 em pacientes com adenocarcinoma do estômago / Serum cytokine of il-2, il-10 and il-12 levels in patients with stomach adenocarcinoma

ABSTRACT BACKGROUND: Gastric adenocarcinoma is the fourth most common cause of cancer-associated death worldwide. OBJECTIVE: We evaluated the immunological status of patients with gastric cancer before surgery and circulating cytokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 90 healthy controls and 95 patients with distal Gastric adenocarcinoma in Mazandaran, Sari, Iran. We measured serum IL-2, IL-10 and IL-12 Levels by a sandwich enzyme-linked immunosorbent assay using the IBL international GMBH kit. RESULTS: The serum IL-10 levels in the patients with Gastric adenocarcinoma were significantly higher than those of the healthy controls (P=0.02). There were no significant differences in serum IL-2 and IL-12 levels between patients with gastric cancer and healthy controls. CONCLUSION: Increased levels of IL-10 might be useful as diagnostic biomarkers for Gastric adenocarcinoma; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. These results suggest that positive expression of IL-10 may be useful as a molecular marker to distinguish stage of gastric cancers which can be more readily controlled.

RESUMO CONTEXTO: O adenocarcinoma gástrico é a quarta causa mais comum de morte relacionada ao câncer em todo o mundo. OBJETIVO: Avaliar o status imunológico dos pacientes com câncer gástrico antes da cirurgia e as citocinas circulantes como potenciais biomarcadores diagnósticos para câncer gástrico. MÉTODOS: Incluímos 90 indivíduos controles saudáveis e 95 pacientes com adenocarcinoma gástrico distal em Mazandaran, Sari, Iran. Os níveis de soro Il-2, IL-10 e Il-12 foram medidos por um ensaio de imunoabsorção enzimática pela técnica de sanduíche usando o kit IBL International GmbH. RESULTADOS: Os níveis séricos IL-10 nos pacientes com adenocarcinoma gástrico foram significativamente superiores aos dos controles saudáveis (P=0,2). Não houve diferenças significativas nos níveis de soro IL-2 e IL-12 entre pacientes com câncer gástrico e controles saudáveis. CONCLUSÃO: Níveis aumentados de IL-10 podem ser úteis como biomarcadores diagnósticos para adenocarcinoma gástrico; no entanto, isso precisa ser confirmado com maior número de pacientes e com grupos de controle que não sejam doadores de sangue, adequadamente emparelhado por idade. Estes resultados sugerem que a expressão positiva do IL-10 pode ser útil como um marcador molecular para distinguir a fase de câncer gástrico que pode ser mais facilmente controlada.

SERUM CYTOKINE OF IL-2, IL-10 AND IL-12 LEVELS IN PATIENTS WITH STOMACH ADENOCARCINOMA.

BACKGROUND: Gastric adenocarcinoma is the fourth most common cause of cancer-associated death worldwide. OBJECTIVE: We evaluated the immunological status of patients with gastric cancer before surgery and circulating cytokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 90 healthy controls and 95 patients with distal Gastric adenocarcinoma in Mazandaran, Sari, Iran. We measured serum IL-2, IL-10 and IL-12 Levels by a sandwich enzyme-linked immunosorbent assay using the IBL international GMBH kit. RESULTS: The serum IL-10 levels in the patients with Gastric adenocarcinoma were significantly higher than those of the healthy controls (P=0.02). There were no significant differences in serum IL-2 and IL-12 levels between patients with gastric cancer and healthy controls. CONCLUSION: Increased levels of IL-10 might be useful as diagnostic biomarkers for Gastric adenocarcinoma; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. These results suggest that positive expression of IL-10 may be useful as a molecular marker to distinguish stage of gastric cancers which can be more readily controlled.