Evaluation of the hematological and immunological markers after the first and second doses of BNT162b2 mRNA vaccine.

OBJECTIVE: Both humoral and cellular immunity can be significantly influenced by the immunological responses to vaccination, and both responses are essential. Vaccination is the most consistent, safe, and cost-efficient practice for controlling the COVID-19 pandemic. PATIENTS AND METHODS: Blood samples were collected from participants who received two vaccine doses of COVID-19 Pfizer/BioNTech (BNT162b2) before and on days 7 and 10 after the first and second immunization. We evaluated some hematological and immunological markers responses to the 1st and 2nd doses of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine. RESULTS: In healthy subjects' neutrophil and WBC counts significantly increased compared to those after the first dose. The results of all first-group participant categories demonstrated no discernible variations in lymphocyte counts. There was no change in IgM or IgG in all second-group cohorts, except for a considerable rise in IgG levels in people with a history of coronavirus infection following the second dosage compared to baseline. After the second dose, CD4+ T-cell and CD8+ T-cell levels rose in all groups compared to before the immunization and after the first dosage. Data demonstrated a substantial rise in neutrophil-lymphocyte ratio (NLR) after the second dose of the vaccine. Individuals who had previously had COVID-19 disease experienced a considerable increase in C3 and C4 levels after the first and second dosages compared to baseline. Additionally, compared to their levels after the first dosage, C4 levels increased significantly following the second dosage. Interleukin (IL)-6, IL-15, macrophage colony-stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10/CXCL10), and macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) levels were increased after boost correlated with Spike antibody levels, supporting their utility as indicators of successful humoral immunity development in response to vaccination. CONCLUSIONS: We can conclude that the Pfizer/BioNTech vaccine produced a more potent T-cell response than humoral ones.

The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19. PATIENTS AND METHODS: In this prospective cohort study, 60 hospitalized T2DM patients with COVID-19 on metformin plus standard anti-COVID-19 treatments compared to 40 hospitalized T2DM patients with COVID-19 on other diabetic pharmacotherapy like insulin and sulfonylurea, were recruited. Inflammatory and oxidative stress biomarkers and radiological and clinical outcomes were assessed at admission time and at the time of discharge. RESULTS: The results of this study illustrated that metformin treatment in T2DM patients with COVID-19 was more effective in reducing inflammatory and oxidative stress biomarkers with significant amelioration of radiological scores and clinical outcomes compared to T2DM patients with COVID-19 on another diabetic pharmacotherapy. CONCLUSIONS: Our findings highlighted that metformin efficiently managed T2DM patients with COVID-19 by reducing inflammatory and oxidative stress with mitigating effects on the radiological scores and clinical outcomes.

CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA genes expression in colorectal cancer patients: novel diagnostic biomarkers.

OBJECTIVE: This study aimed to investigate the CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA mRNA expression in the blood of colorectal cancer patients in Egypt. This was performed to elucidate if there's a link between this gene expression and other clinicopathological characteristics of the tumor. PATIENTS AND METHODS: A case-control study including 50 colorectal cancer patients and 50 healthy controls was conducted. Real-time polymerase chain reaction (rt-PCR) was utilized to assess the expression of CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA mRNA in blood samples. RESULTS: Patients with colorectal cancer had significantly higher levels of mRNA for the genes CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA (p<0.001, p=0.021, p<0.001, and p<0.001, respectively) compared to controls. Remarkedly, the gene expression of AHR, TRIP13, and PIK3CA genes did not exhibit a significant correlation with the tumor stages (p=0.379, p=0.095, and p=0.526, respectively). However, there was a strong correlation between CYP24A1 and CPEB4 gene expression and tumor stages (p<0.001 and p=0.002, respectively). CONCLUSIONS: Therefore, we can conclude that increased mRNA levels of CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA in blood samples withdrawn from colorectal cancer patients could be a biomarker for the disease.

Elucidation of the role of α-lipoic acid and vitamin C in methotrexate-induced hepatoxicity in mice.

OBJECTIVE: Although methotrexate (MTX) is used to treat several malignancies and chronic inflammatory diseases, its clinical use is constrained because of its negative side effects, the most prevalent of which are hepatotoxicity and nephrotoxicity. So, this study aims to determine whether α-lipoic acid (ALA) and vitamin C can protect mice against the liver damage that methotrexate causes. MATERIALS AND METHODS: A total of 49 male mice were divided into seven groups at random. Group I received sodium bicarbonate, while groups II to VII received an intraperitoneal injection of MTX (20 mg/kg) on the tenth day, following ten days of pretreatment with ALA (60 mg/Kg), ALA (120 mg/Kg), vitamin C (100 mg/Kg), vitamin C (200 mg/Kg), ALA (60 mg/Kg), and vitamin C (100 mg/kg). RESULTS: When compared to mice in group I, mice in group II (the control group) had significantly higher levels of the enzymes malondialdehyde (MDA), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significantly lower (p <0.05) levels of the enzymes superoxide dismutase (SOD) and glutathione (GSH). As compared to the control group, pretreatment groups with ALA and vitamin C showed a dose-dependent substantial rise (p <0.05) in GSH and SOD levels, a dose-dependent notable decrease (p <0.05) in MDA, ALT, ALP, and LDH levels, and better liver histological architecture. In order to increase the antioxidant capacity, pretreatment with ALA and vitamin C may be able to prevent MTX-induced hepatotoxicity. CONCLUSIONS: These results imply that ALA and vitamin C are useful in the treatment of MTX-induced liver damage.

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits / Efeitos protetores de Zizyphus oxyphyla em biomarcadores de soro relacionados ao fígado e rim em (CCl4) intoxicam rabbtis

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P < 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P < 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P < 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P < 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits

Abstract The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P 0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P 0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P 0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

Resumo O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Possible mechanistic insights into iron homeostasis role of the action of 4-aminoquinolines (chloroquine/hydroxychloroquine) on COVID-19 (SARS-CoV-2) infection.

OBJECTIVE: With the recent direction in drug repurposing, many approved drugs have been evaluated to assess their effect on the coronavirus or SARS-CoV-2 infection (COVID-19). Driving this path, chloroquine (CQ) has been used in the treatment of malaria and hydroxychloroquine (HCQ) in immunomodulatory and anti-thrombotic action, playing a leading role in initial management of the viral infection. MATERIALS AND METHODS: Literature search was done using Google Scholar, PubMed and Scopus database using keywords "chloroquine" "SARS-CoV-2" "COVID-19" "mechanism of action" and articles of interest were selected providing evidence of the possible role of CQ in viral infection. RESULTS: In a bid to understand how and if CQ and HCQ would exert their anti-viral property, mechanistic exegesis was done to review various proposed mechanisms of action. This revealed the inhibition of viral attachment and entry, inhibition of enveloped glycoprotein, inhibition of the development and proliferation of new viral particles as the way they perform their action. There is an interplay between iron metabolism and homeostasis with COVID-19 infection and viral reproduction. CONCLUSIONS: This study aims to show the functional role of CQ and HCQ, as well as to provide possible mechanistic insight on the role of iron on viral infection, iron starvation and its downstream cellular pathways involving hepcidin and proinflammatory cytokines. The overall aim of providing possible mode of action of CQ and HCQ in the management of COVID-19 infection is exhibited via its anti-viral, anti-inflammatory and anti-thrombotic activities.

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits.

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

The potential mechanistic insights and future implications for the effect of prebiotics on poultry performance, gut microbiome, and intestinal morphology.

Prebiotics may modify the biological processes in the chickens' gastrointestinal tract to improve poultry performance and health. Prebiotics are natural feed additives that offer many economic advantages by decreasing mortality rates, increasing growth rates, and improving birds' feed efficiency. Prebiotic action potentially affects the degradation of indigestible dietary compounds, the synthesis of nitrogen components and vitamins, and simplifies the removal of undesirable elements in the diet. Prebiotics could also induce desirable gut microbiome modifications and affect host metabolism and immune health. It is worth mentioning that gut bacteria metabolize the prebiotic compounds into organic compounds that the host can subsequently use. It is important to limit the concept of prebiotics to compounds that influence the metabolism of resident microorganisms. Any medicinal component or feed ingredient beneficial to the intestinal microecosystem can be considered a prebiotic. In this review, the impacts of prebiotics on the gut microbiome and physiological structure are discussed, emphasizing the poultry's growth performance. The current review will highlight the knowledge gaps in this area and future research directions.