MYELOID-DERIVED SUPPRESSOR CELLS TWO YEARS AFTER HEPATITIS C VIRUS ERADICATION USING DIRECTLY ACTING ANTIVIRALS.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. OBJECTIVE: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. METHODS: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. RESULTS: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001). CONCLUSION: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.

Assessment of serum proprotein convertase subtilisin/kexin type 9 in pediatric sepsis syndrome.

Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its tissues and organs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme released in response to the drop in cholesterol level occurring in sepsis. Our study aimed to evaluate the prognostic role of serum Proprotein convertase subtilisin/kexin type 9 (PCSK9) level in children with sepsis and severe sepsis. Sixty children were included in this study. They were divided into two groups: 30 children in the sepsis group and 30 in the severe sepsis group. Another 30 apparently healthy children were included as a control group. Blood samples were withdrawn from all included children for complete blood count (CBC), renal function tests (RFT), liver function tests (LFT), LDL-cholesterol (LDL-C), blood culture, and serum PCSK9. In this study, PCSK9 and LDL-C were higher in the two sepsis groups than in the control group (p < 0.05). They were also higher in the severe sepsis group than the sepsis group and in the non-survivors than in the survivors (p < 0.05). PCSK9 was positively correlated with length of hospital stay in surviving children (r = 0.67, p = 0.001) and had predicted significant hematological dysfunction (adjusted B = - 96.95, p = 0.03). In conclusion, the PCSK9 assay can be used as a biomarker for bad prognosis in children suffering from clinical sepsis.

Exploring the NRF2/HO-1 and NF-κB Pathways: Spirulina Nanoparticles as a Novel Approach to Combat Diabetic Nephropathy.

Arthrospira platensis has been the subject of plentiful studies due to its purported health advantages; nevertheless, additional investigation is required to determine whether several chronic diseases may be treated or avoided with its nanoform. Therefore, we set out to examine A. platensis nanoparticles (SNPs) to protect against kidney impairment caused by Streptozotocin (STZ) in diabetic rats, precisely focusing on its effect and the cellular intracellular pathways involved. Male Wistar rats were assigned into four groups: Group 1 was set as control, comprising the normal rats; group 2 was administered SNPs (0.5 mg/kg BW, once/day) orally for 84 consecutive days; group 3, STZ-diabetic rats were injected with STZ (65 mg/kg BW); and group 4, in which the diabetic rats were treated with SNPs. After inducing diabetes in rats for 84 days, the animals were euthanized. The results disclosed that SNP treatment substantially (P < 0.05) improved the glucose and glycated hemoglobin levels (HbA1c %), insulin, C-peptide, and cystatin C deterioration in diabetic rats. Furthermore, SNP administration significantly lowered (P < 0.05) nitric oxide (NO) and malondialdehyde (MDA) levels in renal tissue and enhanced kidney function metrics, as well as improved the antioxidant capacity of the renal tissue. In addition, oral SNPs overcame the diabetic complications concerning diabetic nephropathy, indicated by downregulation and upregulation of apoptotic and antiapoptotic genes, respectively, along with prominent modulation of the antiangiogenic marker countenance level, improving kidney function. SNP modulated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 (NRF2/HO-1) pathways and inhibited the nuclear factor-κB (NF-κB) expression, strengthening the SNP pathways in alleviating diabetic nephropathy. The histopathology results corroborated the obtained biochemical and molecular observations, suggesting the therapeutic potential of SNPs in diabetic nephropathy via mechanisms other than its significant antioxidant and hypoglycemic effects, including modulation of antiangiogenic and inflammatory mediators and the NRF2/HO-1 pathways.

Access to mifepristone, misoprostol, and contraceptive medicines in eight countries in the Eastern Mediterranean Region: descriptive analyses of country-level assessments.

BACKGROUND: Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited. METHODS: A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020-2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted. RESULTS: Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs-and registered-in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia). CONCLUSION: These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines' availability were permitted under national law and where culturally acceptable.

Ensuring access to Mifepristone, Misoprostol, and contraceptive medicines is critical to improving women's health, and more specifically reducing maternal mortality and improving women's sexual and reproductive health in the Eastern Mediterranean Region.The aim of this study was to analyse findings from national assessments to capture information on the implementation of relevant policies and procedures. Those were the policies that ensure access to Mifepristone, Misoprostol, and contraceptive medicines in the public sector for the eight Eastern Mediterranean Region countries included in the study (Afghanistan, Iraq, Libya, Lebanon, Morocco, Palestine, Pakistan, and Somalia). The assessments were completed between 2020 and 2021.We found that most countries did not include all twelve contraceptives enlisted in the WHO essential medicines list (EML) in their national family planning guidelines. No country had developed a national abortion care guidelines nor included mifepristone (alone or in combination with misoprostol) on national EML. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs­and registered­in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan) yet, only three countries procured misoprostol (Iraq, Morocco, and Somalia).Our findings provide evidence on system-level barriers to availability of Mifepristone, Misoprostol, and contraceptive medicines (e.g., lack of guidelines or inclusion on EML, lack of registration and procurement) that can support policy and advocacy efforts to strengthen the pharmaceutical sector to better ensure availability of Mifepristone, Misoprostol, and contraceptive medicines to women in reproductive age at the country-level in accordance with the national law and prevailing culture.

A systematic review of mental health of women in fragile and humanitarian settings of the Eastern Mediterranean Region.

Background: The increasing emergencies and humanitarian challenges have worsened the mental health condition of women in the Eastern Mediterranean Region. Aim: To assess the prevalence, determinants and interventions to address mental health among women in fragile and humanitarian settings in the Eastern Mediterranean Region. Methods: Using the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines, we reviewed 59 peer-reviewed published studies (PubMed, IMEMR) and grey literature (WHO/IRIS) from January 2001 to February 2023, focusing on women's mental health in the Eastern Mediterranean Region. We then conducted a descriptive analysis of the sociodemographic characteristics. Results: Among the 59 studies reviewed, only 13 of the 48 peer-reviewed studies focused primarily on women's mental health, 11 grey literature records mostly presented grouped regional data, 11 of the 25 studies on mental health among migrants were about those taking refuge in high-income countries. The average prevalence of mental disorders from 32 cross-sectional studies on women aged 12-75 years was 49%, average prevalence of anxiety was 68%, post-traumatic stress disorder was 52%, and depression was 43%. Women exhibited higher level depression than men. Age, educational disparities, and limited access to services were important risk factors for mental health disorder. Several promising interventions emerged. Conclusion: More efforts should be made to provide customized, context-specific solutions to the mental health challenges of women in humanitarian and fragile settings in the Eastern Mediterranean Region, including allocation of more resources to mental health programmes, addressing barriers, enhancing mental health surveillance, and reduction of stigma.

Células supressoras mieloides derivadas dois anos após a erradicação do vírus da hepatite C usando antivirais de ação direta / Myeloid-derived suppressor cells two years after hepatitis c virus eradication using directly acting antivirals

ABSTRACT Background: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. Objective: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. Methods: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. Results: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001). Conclusion: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.

RESUMO Contexto: As células supressoras derivadas de mieloides (CSDMs) possuem morfologia imatura, atividade fagocítica relativamente fraca e algumas funções imunossupressoras. A capacidade das CSDMs de inibir respostas imunológicas mediadas por células T é sua característica funcional mais notável. A expansão e ativação das CSDMs contribuem significativamente para a ocorrência e progressão de tumores, regulando negativamente a vigilância imunológica antitumoral. Níveis aumentados de CSDMs em pacientes com infecção crônica pelo vírus da hepatite C (HCV) poderiam suprimir respostas das células T, promovendo a fuga viral e a progressão da hepatite. Isso pode tornar os indivíduos infectados pelo HCV mais vulneráveis a infecções graves, tumores hepáticos e extra-hepáticos, e a uma capacidade diminuída de reagir à imunização. Ainda não se sabe se a erradicação eficaz do HCV com antivirais de ação direta (AAD) pode restaurar as funções imunológicas e a capacidade de vigilância imunológica. Objetivo: O objetivo deste estudo foi observar a frequência de M-CSDMs (CD33+, CD11b+ e HLA-DR-) em pacientes com histórico anterior de HCV, 2-3 anos após a erradicação do vírus usando terapia com AADs. Métodos: Este estudo foi realizado em 110 indivíduos: 55 indivíduos sem cirrose hepática que foram tratados com AADs para HCV e atingiram resposta virológica sustentada (SVR) por um período de 2-3 anos e 55 controles saudáveis pareados por idade e gênero. O estudo foi conduzido no período de janeiro a julho de 2022. Os pacientes foram recrutados da Unidade Nacional de Tratamento de Hepatites Virais, da clínica ambulatorial de Hepatologia da Universidade de Alexandria e da clínica ambulatorial de Medicina Tropical da Universidade de Alexandria. As frequências de CSDMs (CD33+CD11b+HLA-DR-) foram avaliadas por citometria de fluxo. Resultados: Mesmo após a erradicação do vírus por mais de dois anos, os níveis de CSDMs em indivíduos tratados para HCV foram consideravelmente mais altos. No grupo tratado para HCV, o número mediano de CSDMs foi de 5, com um intervalo interquartil (IQR) de 3,79-7,69. Em contraste, a mediana para o grupo controle foi de 3,1, com um IQR de 1,4-3,2 (P<0,001). Conclusão: A terapia bem-sucedida com AADs leva a uma reconstituição imunológica lenta e parcial, como demonstrado pela falha em atingir níveis normais de CSDMs 2 anos após a erradicação bem-sucedida do HCV, apesar da normalização dos parâmetros laboratoriais e da ausência de fibrose hepática. As implicações clínicas desses achados devem ser estudadas minuciosamente.

Data extraction and comparison for complex systematic reviews: a step-by-step guideline and an implementation example using open-source software.

BACKGROUND: Data extraction (DE) is a challenging step in systematic reviews (SRs). Complex SRs can involve multiple interventions and/or outcomes and encompass multiple research questions. Attempts have been made to clarify DE aspects focusing on the subsequent meta-analysis; there are, however, no guidelines for DE in complex SRs. Comparing datasets extracted independently by pairs of reviewers to detect discrepancies is also cumbersome, especially when the number of extracted variables and/or studies is colossal. This work aims to provide a set of practical steps to help SR teams design and build DE tools and compare extracted data for complex SRs. METHODS: We provided a 10-step guideline, from determining data items and structure to data comparison, to help identify discrepancies and solve data disagreements between reviewers. The steps were organised into three phases: planning and building the database and data manipulation. Each step was described and illustrated with examples, and relevant references were provided for further guidance. A demonstration example was presented to illustrate the application of Epi Info and R in the database building and data manipulation phases. The proposed guideline was also summarised and compared with previous DE guidelines. RESULTS: The steps of this guideline are described generally without focusing on a particular software application or meta-analysis technique. We emphasised determining the organisational data structure and highlighted its role in the subsequent steps of database building. In addition to the minimal programming skills needed, creating relational databases and data validation features of Epi info can be utilised to build DE tools for complex SRs. However, two R libraries are needed to facilitate data comparison and solve discrepancies. CONCLUSIONS: We hope adopting this guideline can help review teams construct DE tools that suit their complex review projects. Although Epi Info depends on proprietary software for data storage, it can still be a potential alternative to other commercial DE software for completing complex reviews.

A rare rotated, medially displaced fracture-dislocation of the medial clavicle - Case report and review of the literature.

Clavicle fractures combined with sternoclavicular joint dislocations are very rare injuries that need to be addressed quickly and treated effectively due to the altered biomechanics of the shoulder girdle as well as to the potential damages to the surrounding "noble" anatomical structures. A diagnostic and therapeutic algorithm for such injuries has not yet been established. Computer Tomography with 3D reconstruction should be the diagnostic gold standard. In case of a highly displaced fracture and/or dislocation in an active patient, surgical treatment is advised in order to obtain proper bone and joint healing with satisfactory functional outcomes as well as to protect the surrounding anatomical structures from potential damages. We present the case of an 18-year-old male, skeletally mature patient, who had a fall while snowboarding. Subsequently he was diagnosed with a very uncommon combination of a displaced medial clavicle fracture and complete posterior Sterno-Clavicular dislocation with 111° rotation of the sternoclavicular fragment. We opted for surgery, decided to use "off-label" a 2.5 V-plate Ulna plate long (Medartis®) and to associate this procedure with a Sterno-Clavicular arthrodesis with tape-augmentation to stabilize the SC joint; this treatment strategy resulted in a good clinical outcome without any remaining instability and satisfactory ROM. We collected this case to describe this seldom combination, to show our treatment strategy and to advocate the creation of a standardized diagnostic and therapeutic algorithm. X-rays, Computer Tomography images and intraoperative photos are presented.

Retraction to "Silver-Doped Cadmium Selenide/Graphene Oxide-Filled Cellulose Acetate Nanocomposites for Photocatalytic Degradation of Malachite Green toward Wastewater Treatment".

[This retracts the article DOI: 10.1021/acsomega.1c02667.].

Effect of coconut oil on growth performance, carcass criteria, liver and kidney functions, antioxidants and immunity, and lipid profile of broilers.

The aim of this study is to evaluate the beneficial effects of coconut essential oil on growth performance, carcass criteria, antioxidant status, and immune response of broiler chicks. A total of 192 un-sexed 7-days broiler chicks were divided into six treatment sets with four copies of 8 chicks per set. The groups were as follows: (1) basal diet (without additive), (2) basal diet plus 0.5 ml coconut essential oil/kg, (3) basal diet plus 1 ml coconut essential oil/kg, (4) basal diet plus 1.5 ml coconut essential oil/kg, (5) basal diet plus 2 ml coconut essential oil/kg and (6) basal diet plus 2.5 ml coconut essential oil/kg. The results showed that the most prevalent compound in coconut oil is 6-Octadecenoic acid (oleic acid) representing 46.44% followed 2(3H)-Furanone, dihydro-5-pentyl- (CAS) (11.36%), Hexadecanoic acid (CAS) (4.71%), and vanillin (2.53%). Dietary 1 and 1.5 ml of coconut oil improved significantly the body weight and gain of broiler chickens. Dietary supplementation of 1 ml of coconut oil improved significantly liver function compared to control and other treatment groups. The supplementation with 1 ml coconut oil significantly reduced TG and VLDL compared to control and other treatment groups, while no significant differences in TC, HDL, and LDL due to dietary coconut oil. The present findings showed that dietary coconut oil with 1 and 1.5 ml/kg feed improved significantly antioxidants status through increased antioxidant enzymes like SOD and GSH while decreasing significantly MDA levels compared to control and other treatment groups. Therefore, it was concluded that the diets of broiler chickens could be fortified with coconut oil with 1 or 1.5 ml to improve the growth, feed utilization, and antioxidant status of broiler chickens.

Interplay between cross sectional analysis of risk factors associated with Toxoplasma gondii infection in pregnant women and their domestic cats.

Toxoplasmosis is a global zoonotic disease caused by Toxoplasma gondii (T. gondii). The primary aim of this study was to identify hygienic and cat management practices that could affect the occurrence of T. gondii in cats and their owners in Sharqia Governorate, Egypt. T. gondii infection was evaluated in 80 pregnant women and 29 domestic cats using Real-time PCR. A questionnaire was administered to obtain information regarding the risk factors associated with T. gondii infection. Blood samples were collected from enrolled pregnant women, and fecal samples were collected from their pet cats. Firth logistic regression model complemented with random forest (RF) analysis was used to evaluate the association of different hygiene and cat management practices with T. gondii infection in pregnant women. T. gondii infection was identified in 27.5% of pregnant women and 17% of domestic cats. Drinking raw milk and contacting stray and pet cats were significantly associated with higher odds of T. gondii infection. The proportion of T. gondii-positive women who ate raw meat (60.0%) was higher than those ate heat-cooked meat (25.3%). Moreover, women who did not wash their hands after contact with cats were 6 times (OR 6.12; CI: 3.03-9.21) more likely to experience T. gondii infection than those washed their hands after cat contact. The RF analysis showed that washing hands constitute a serious yet preventable public health concern that requires targeted, community-specific efforts. Cat owners, particularly pregnant women, need to be aware about the risk of T. gondii infection, while handling cat and pet's owner should be advised to take necessary hygienic measures to prevent its infection.

Citrus Waste as Source of Bioactive Compounds: Extraction and Utilization in Health and Food Industry.

The current research was conducted to extract the bioactive compounds from citrus waste and assess their role in the development of functional foods to treat different disorders. The scientific name of citrus is Citrus L. and it belongs to the Rutaceae family. It is one of the most important fruit crops that is grown throughout the world. During processing, a large amount of waste is produced from citrus fruits in the form of peel, seeds, and pomace. Every year, the citrus processing industry creates a large amount of waste. The citrus waste is composed of highly bioactive substances and phytochemicals, including essential oils (EOs), ascorbic acid, sugars, carotenoids, flavonoids, dietary fiber, polyphenols, and a range of trace elements. These valuable compounds are used to develop functional foods, including baked products, beverages, meat products, and dairy products. Moreover, these functional foods play an important role in treating various disorders, including anti-aging, anti-mutagenic, antidiabetic, anti-carcinogenic, anti-allergenic, anti-oxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective activity. EOs are complex and contain several naturally occurring bioactive compounds that are frequently used as the best substitutes in the food industry. Citrus essential oils have many uses in the packaging and food safety industries. They can also be used as an alternative preservative to extend the shelf lives of different food products.

Cell Growth Inhibition, DNA Fragmentation and Apoptosis-Inducing Properties of Household-Processed Leaves and Seeds of Fenugreek (Trigonella Foenum-Graecum Linn.) against HepG2, HCT-116, and MCF-7 Cancerous Cell Lines.

Household processing of fenugreek seeds and leaves, including soaking, germination, and boiling of the seeds, and air-drying of the leaves, has improved the levels of human consumption of the bitter seeds and increased the shelf life of fresh leaves, respectively. The potential anticancer activity of either unprocessed or processed fenugreek seeds or leaves and the relative expression of pro-apoptotic and anti-apoptotic genes of the studied cancerous cell lines exposed to IC50 crude extracts was investigated to observe the apoptotic-inducing property of this plant as an anticancer agent. The protein expression of IKK-α and IKK-ß, as inhibitors of NF-KB which exhibit a critical function in the regulation of genes involved in chronic inflammatory disorders, were studied in the tested cancerous cell lines. In this study, the anticancer activity of household-processed fenugreek leaves and seeds against HepG2, HCT-116, MCF-7, and VERO cell lines was measured using an MTT assay. DNA fragmentation of both HepG2 and MCF-7 was investigated by using gel electrophoresis. RT-PCR was used to evaluate the relative expression of each p53, caspase-3, Bax, and Bcl-2 genes, whereas ELISA assay determined the expression of caspase-3, TNF-α, and 8-OHDG genes. Western blotting analyzed the protein-expressing levels of IKK-α and IKK-ß proteins in each studied cell line. Data showed that at 500 µg mL-1, ADFL had the highest cytotoxicity against the HepG2 and HCT-116 cell lines. Although, each UFS and GFS sample had a more inhibitory effect on MCF-7 cells than ADFL. Gel electrophoresis demonstrated that the IC50 of each ADFL, UFS, and GFS sample induced DNA fragmentation in HepG2 and MCF-7, contrary to untreated cell lines. Gene expression using RT-PCR showed that IC50 doses of each sample induced apoptosis through the up-regulation of the p53, caspase-3, and Bax genes and the down-regulation of the Bcl-2 gene in each studied cell line. The relative expression of TNF-α, 8-OHDG, and caspase-3 genes of each HepG2 and MCF-7 cell line using ELISA assays demonstrated that ADFL, UFS, and GFS samples reduced the expression of TNF-α and 8-OHDG genes but increased the expression of the caspase-3 gene. Protein-expressing levels of IKK-α and IKK-ß proteins in each studied cell line, determined using Western blotting, indicated that household treatments decreased IKK-α expression compared to the UFS sample. Moreover, the ADFL and SFS samples had the most activity in the IKK-ß expression levels. Among all studied samples, air-dried fenugreek leaves and unprocessed and germinated fenugreek seeds had the most anti-proliferative and apoptotic-inducing properties against human HepG2, MCF-7, and HCT-116 cell lines, as compared to the VERO cell line. So, these crude extracts can be used in the future for developing new effective natural drugs for the treatment of hepatocellular, breast, and colon carcinomas.

GC-MS Analysis of Bioactive Compounds Extracted from Plant Rhazya stricta Using Various Solvents.

Worldwide, human beings have traditionally employed many folkloric herbal resources as complementary and alternative remedies, and these remedies have played a pivotal role in modern medicines for many decades, as scientists have used them to develop drugs. We studied the effects of employing solvents with varying polarity on the yields of phytochemical components extracted from the plant Rhazya stricta. We used chloroform-methanol (1:1), methanol, ethanol, diethyl ether, and ethyl acetate as extraction solvents. The results showed that the efficiencies of the solvents at extracting phytochemical compounds were in this order: chloroform-methanol < ethanol < methanol < diethyl ether < ethyl acetate extract. The chloroform-methanol extract produced the highest concentration of phenolic and flavonoid contents among the five solvents tested (13.3 mg GAE/g DM and 5.43 CE/g DM). The yields of the extracted phytochemical compounds ranged from 47.55 to 6.05%. The results revealed that the properties of the extraction solvents considerably impacted the extraction yield and the phytochemical components of the R. stricta extract. Furthermore, compared with the other solvents, the chloroform-methanol extraction led to the highest yield (47.55%) and to more phytochemical substances being extracted. The aim of this study is to investigate the phytochemical compounds extracted from R. stricta with different solvents that have different polarities.

To seal or not to seal following an antimicrobial infusion at dry-off? A systematic review and multivariate meta-analysis of the incidence and prevalence of intramammary infections post-calving in dairy cows.

Teat sealants (TSs) consist of sterile formulations with no antibacterial activity. Alone or in combination with antimicrobial (AM) or non-AM treatments, TSs have been commonly used in dairy cows at dry-off to prevent intra-mammary infections (IMIs) during the dry period. This study aimed to identify and synthesise the available evidence on the efficacy of combining TSs with AM treatments on the incidence and prevalence of IMIs. A comprehensive search of three electronic databases, two relevant conference proceedings, and reference lists of reviews and eligible articles was conducted to retrieve and identify studies that could answer the following question: in dairy cows, how does the efficacy of an AM-TS combination administered at dry-off compare with an AM alone for preventing new IMI? In addition to the general IMIs, bacterial species-specific data were extracted and combined into nine distinct pathogen groups: coagulase-positive and negative staphylococci; S. dysgalactiae; non-dysgalactiae Streptococci; E. coli; non-E. coli Enterobacteriaceae; Corynebacterium spp.; yeast and other frequent mastitis pathogens. The structural relationship between each study's prevalence and incidence, as the new (incidence) and persistent (uncured) infections make up the prevalence, was utilised to approximate a variance-covariance matrix for the within-study correlation between their study-specific log odds ratios (ORs). A bivariate random-effects meta-analysis was employed, utilising the within- and between-study correlations to synthesise both outcomes simultaneously. The risk of bias was assessed using the Cochrane ROBINS-I tool, and the quality of the body of evidence was rated using the GRADE approach. A total of 17 trials (16 studies), providing either IMIs incidence (n = 4), prevalence (n = 3) or both (n = 10), were identified. Overall, quarters infused with AM-TS combinations showed lower odds of new IMIs post-calving (OR=0.70; 95% CI=0.57-0.86; Wald test P < 0.001) than those which received only AMs. Across the pathogen groups, varying levels of reduction of new IMIs were found, where administration of TSs was most effective against S. dysgalactiae (OR=0.47; 95% CI=0.23-0.98), non-dysgalactiae streptococci (OR=0.60; 95% CI=0.49-0.74), E. coli (OR=0.62; 95% CI=0.50-0.77), Corynebacterium spp. (OR=0.68; 95% CI=0.52-0.90) and coagulase-negative staphylococci (OR=0.85; 95% CI=0.76-0.94). However, additional TS infusion did not significantly reduce new IMIs in the remaining pathogen groups. The current meta-analytic evidence supports the efficacy of using TS add-on infusions in dairy cows at dry-off for reducing the incidence and prevalence of IMIs post-calving; however, pathogen group differences should be considered.

Effect of Direct Acting Antivirals (DAAs) on Myeloid-Derived Suppressor Cells Population in Egyptian Chronic Hepatitis C Virus Patients: A Potential Immunomodulatory Role of DAAs.

Chronic hepatitis C is a major health concern with high morbidity and mortality rates. The introduction of direct acting antivirals (DAAs) as a first-line treatment for hepatitis C virus (HCV) has significantly enhanced HCV eradication. However, DAA therapy is facing rising concerns regarding long-term safety, viral resistance, and reinfection. HCV is associated with different immune alteration mechanisms that can evade immunity and establish persistent infection. One of these suggested mechanisms is the accumulation of myeloid-derived suppressor cells (MDSCs), which is known to accumulate in chronic inflammatory conditions. Moreover, the role of DAA in restoring immunity after successful viral eradication is still unclear and needs further investigations. Thus, we aimed to investigate the role of MDSCs in chronic HCV Egyptian patients and its response to DAA in treated compared with untreated patients. Fifty untreated chronic hepatitis C (CHC) patients, 50 DAA-treated CHC patients, and 30 healthy individuals were recruited. We used flow cytometer analysis to measure MDSCs frequency and enzyme-linked immunosorbent assay analysis to evaluate the serum level of interferon (IFN)-γ. We found a significant elevation in MDSC% among the untreated group (34.5 ± 12.4%) compared with the DAA-treated group (18.3 ± 6.7%), while the control group had a mean of (3.8 ± 1.6%). IFN-γ concentration was higher in treated patients compared with untreated. We also found a significant negative correlation (rs -0.662) (p < 0.001) between MDSC% and IFN-γ concentration among treated HCV patients. Our results revealed important evidence of MDSCs accumulation in CHC patients and partial retrieval of the immune system regulatory function after DAA therapy.

In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth.

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.

Growth responses and genetic variation among highly ecologically diverse spring wheat genotypes grown under seawater stress.

Most of the freshwaters worldwide are used for agriculture. Freshwater sources are expected to decline and will not suffice to support the food production needed for the growing population. Therefore, growing crops with seawater might constitute a solution. However, very little work has been done on the effect of seawater stress on wheat, an important cereal crop. The present study aimed to determine whether particular wheat genotypes provided better resistance to seawater stress. A set of 80 highly diverse spring wheat genotypes collected from different countries in Europe, Asia, Africa, North and South America was exposed to 50% seawater stress at the early growth stage. Four seeding shoot and root traits were scored for all genotypes. High genetic variations were found among all genotypes for the epicotyl length (EL), hypocotyl length (HL), number of radicles (NOR), and fresh weight (FW). Eight genotypes with high-performance scores of seedling traits were selected. The correlation analyses revealed highly significant correlations among all traits scored in this study. The strongest correlation was found between the NOR and the other seeding traits. Thus, the NOR might be an important adaptive trait for seawater tolerance. The genetic diversity among all genotypes was investigated based on genetic distance. A wide range of genetic distances among all genotypes was found. There was also a great genetic distance among the eight selected genotypes. In particular, the genetic distance between ATRI 5310 (France) and the other seven genotypes was the greatest. Such high genetic diversity might be utilized to select highly divergent genotypes for crossing in a future breeding program. The present study provides very useful information on the presence of different genetic resources in wheat for seawater tolerance.