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1.
J Clin Med ; 12(17)2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37685802

RESUMO

Whole-body vibration (WBV) training is used for ankle rehabilitation as it stimulates muscle spindles to excite tonic vibration reflexes, and improves muscle strength, power, joint proprioception, balance, and flexibility. Thus, this study aims to determine the impact of whole-body vibration on the degree of the toe angle and the correlation between the toe angle and knee osteoarthritis index during level walking among female university students. A randomized controlled trial was conducted with 42 participants divided into two groups. The control group performed only home-based exercise (HBE) after education, and the study group received WBV with HBE. The functional status of participants to predict osteoarthritis was evaluated using the Western Ontario and McMaster osteoarthritis index (WOMAC), where the toe angle degree and WOMAC index were assessed before and six weeks after training. The results showed a significant improvement in the toe-in angle of HBE + WBV compared to the HBE group (p = 0.02), and in HBE + WBV, an improvement of the toe angle showed a 43% decrease in the WOMAC index (p = 0.001). In conclusion, WBV for the ankle and foot training program positively affected the degree of the toe angle, that directly affected the subtalar and ankle joint mechanics. Trial registration in the Pan African Clinical Trial Registry PACTR202304816093190 (registered retrospectively, date of registration: 18 April 2023).

2.
Int J Mol Sci ; 24(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37762060

RESUMO

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.


Assuntos
Actinidia , Complicações do Diabetes , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Insulinas , Animais , Ratos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Antioxidantes , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Mamíferos
3.
Int J Health Sci (Qassim) ; 17(5): 31-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692994

RESUMO

Objective: We determined the association between sacrum displacement and ground reaction force (GRF) during walking on a level surface and identify the sub-phase of gait cycle most affected by GRF. The kinematic parameters of angular displacement of sacrum bone in three directions were measured and a correlation was derived to integrate the effect of GRF to sacrum displacement. Furthermore, gender variation in the sacrum bone configuration that induces the GRF to shift in one direction was determined. Methods: Forty healthy university students were evaluated for a normal gait pattern using the Qualysys motion capture system or a motion analysis system (MAS). The synchronization between MAS and force plate was done through computer software for the three-dimensional analysis (3D) of the force and angular displacement. Results: A positive correlation in the vertical direction was observed in the early and late phases of the stance phase in females. In males, a positive correlation was demonstrated in the middle and late phase of the stance phase. However, a positive correlation in the anteroposterior direction during the middle part of the stance phase was found only among the male group. Conclusion: Incorporation of strength training exercises help to increase the rotator muscle strength of the trunk and lower extremities in both genders. In the male group, flexors and extensors of the trunk and lower extremities in the middle part need to be focused during strength training, especially for athletes. This would be useful in decreasing the incidence of sports injuries.

4.
Life (Basel) ; 13(8)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37629644

RESUMO

Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC. Whole blood was obtained from four consanguineous families with CC. Genomic DNA was extracted from the blood, and the combination of targeted and Sanger sequencing was used to identify the causative gene. The mutations detected were analyzed in silico for structural and protein-protein interactions to predict their impact on protein activities. The sequencing found a known FYCO1 mutation (c.2206C>T; p.Gln736Term) in autosomal recessive mode in families with CC. Co-segregation analysis showed affected individuals as homozygous and carriers as heterozygous for the mutation and the unaffected as wild-type. Bioinformatics tools uncovered the loss of the Znf domain and structural compactness of the mutant protein. In conclusion, a previously reported nonsense mutation was identified in four consanguineous families with CC. Structural analysis predicted the protein as disordered and coordinated with other structural proteins. The autophagy process was found to be significant for the development of the lens and maintenance of its transparency. The identification of these markers expands the scientific knowledge of CC; the future goal should be to understand the mechanism of disease severity. Ascertaining the genetic etiology of CC in a family member facilitates establishing a molecular diagnosis, unlocks the prospect of prenatal diagnosis in pregnancies, and guides the successive generations by genetic counseling.

5.
Diagnostics (Basel) ; 13(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36980393

RESUMO

INTRODUCTION: The coronavirus (COVID-19) has affected millions of people around the world. COVID-19 patients, particularly those with the critical illness, have coagulation abnormalities, thrombocytopenia, and a high prevalence of intravascular thrombosis. OBJECTIVES: This work aims to assess the prevalence of coagulation disorders and their related symptoms among COVID-19 patients in the Al-Jouf region of Saudi Arabia. SUBJECTS AND METHODS: We conducted a retrospective study on 160 COVID-19 patients. Data were collected from the medical records department of King Abdulaziz Specialist Hospital, Sakaka, Al-Jouf, Saudi Arabia. The socio-demographic data, risk factors, coagulation profile investigation results, symptom and sign data related to coagulation disorders, and disease morbidity and mortality for COVID-19 patients were extracted from medical records, and the data were stored confidentially. RESULTS: Males represented the highest prevalence of COVID-19 infection at 65%; 29% were aged 60 or over; 28% were smokers; and 36% were suffering from chronic diseases, with diabetes mellitus representing the highest prevalence. Positive D-dimer results occurred in 29% of cases, with abnormal platelet counts in 26%. CONCLUSION: Our findings confirm that the dysregulation of the coagulation cascade and the subsequent occurrence of coagulation disorders are common in coronavirus infections. The results show absolute values, not increases over normal values; thus, it is hard to justify increased risk and presence based on the presented data.

6.
Parasitol Int ; 94: 102737, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36736658

RESUMO

Nutritional supplements, particularly vitamin D, have been widely used worldwide in the treatment of various infections, including parasites. This study aimed to evaluate the potential effects of vitamin D3 supplementation on the muscular phase of trichinellosis in experimental animals. Mice were divided as follows: (group I): infected untreated, (group IIa) infected and treated with vitamin D3 for 12 doses beginning 2 weeks before infection and continuing after infection, (group IIb) infected and treated with vitamin D3 for 8 doses beginning on the same day of infection, (group III) normal control, (group IVa) which received vitamin D3 for 12 doses and (group IVb) which received vitamin D3 for 8 doses. Mice were sacrificed 35 days after infection and total muscle larval count, and histopathological examination of muscle samples with immunohistochemical staining of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) were performed. Muscle relative cathelicidin mRNA expression was assessed, as well as serum levels of muscle enzymes CK and LDH, interleukin-4 (IL-4), IL-10, IL-17 and interferon-gamma (INF-γ). Vitamin D3 supplementation significantly reduced muscle larval count, inflammatory cellular infiltration, COX2 and iNOS expression. Furthermore, it increased cathelicidin gene expression, decreased serum levels of CK and LDH and affected serum cytokine levels, increasing serum IL-4 and IL10 levels while decreasing serum INF γ and IL-17. In conclusion, vitamin D3 supplementation has favorable outcomes on the muscle phase of trichinellosis, including anti-inflammatory, antioxidant, and immunomodulatory effects.


Assuntos
Colecalciferol , Triquinelose , Camundongos , Animais , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Triquinelose/tratamento farmacológico , Interleucina-4 , Interleucina-17 , Ciclo-Oxigenase 2 , Catelicidinas , Suplementos Nutricionais , Oxirredução
7.
Int J Mol Sci ; 24(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36769034

RESUMO

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). ß-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of ß-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, ß-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa ß (NF-kß), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kß, on the other hand, significantly decreased. Using ß-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , beta-Glucanas , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Oxazolona , Aldeído Redutase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , beta-Glucanas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , Mitocôndrias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Trifosfato de Adenosina/metabolismo , DNA/metabolismo
8.
Acta Trop ; 239: 106830, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36638878

RESUMO

Toxoplasma gondii is a zoonotic intracellular protozoan parasite and its therapeutic limitations are one of its major problems. L-citrulline is an organic compound that has beneficial effects on many diseases. The purpose of this study was to assess the impact of L-citrulline, alone or in combination with sulfamethoxazole-trimethoprim (SMZ-TMP) on acute toxoplasmosis caused by Toxoplasma gondii RH virulent strain. In our study, 60 Swiss albino mice were divided into two main groups; the control group and the infected treated group, which was subdivided into group IIa: infected treated with L-citrulline, group IIb: infected treated with SMZ-TMP, and group IIc: infected treated with L-citrulline combined with SMZ-TMP. The effects of treatment were assessed by parasitological study, electron microscopic study of tachyzoites, and histopathological study of the liver. Moreover, ELISA measurement of the serum level of Interferon-gamma, Interleukin 10, Nitric oxide, and apoptotic markers was used. It was noticed that L-citrulline combined with SMZ-TMP significantly increased the survival time of infected mice with a significant decrease in the number of tachyzoites compared to the other groups. Moreover, it increased the levels of measured cytokines and serum anti-apoptotic proteins Bcl-2 and improved the extent of liver cell damage associated with a decrease in inflammatory infiltration. In conclusion, L-citrulline supplementation was found to be effective against acute toxoplasmosis, especially when combined with SMZ-TMP as it has multifactorial mechanisms; nitric oxide production, anti-inflammatory, anti-apoptotic, and immune stimulator.


Assuntos
Toxoplasma , Toxoplasmose , Animais , Camundongos , Citrulina/uso terapêutico , Citrulina/farmacologia , Óxido Nítrico , Toxoplasmose/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
9.
ACS Omega ; 7(45): 41627-41640, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36406541

RESUMO

Nanotechnology is the study of materials' unique properties at the nanoscale. Nanomedicine is the application of nanotechnology in medicine, which has been utilized to treat some common diseases, such as cancer. The aim of the present work is to synthesize the cadmium (Cd) nanocomplex using paracetamol as a ligand with a molar ratio of 1:2 M/L that was characterized by different physicochemical methods and to explore the effect of the synthesized Cd nanocomplex on the immune system and the redox status of the body and their anticancer effects on Ehrlich ascites carcinoma (EAC) induced in mice. Eighty female albino mice were separated into Group I: control; Group II: EAC; Group III: EAC treated with a low-dose Cd nanocomplex; and Group IV: EAC treated with a high-dose Cd nanocomplex. Interleukin-6 (IL-6), NLR family pyrin domain containing 3 (NLRP3), and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels were assessed by enzyme-linked immunosorbent assay (ELISA). Peroxynitrite level and glutathione peroxidase activity were assessed by spectrophotometry. NRF2 mRNA expression, cadmium content, and liver and renal toxicity were estimated. Results: There was a significant increase in IL-6, NLRP3, 8-OHdG, peroxynitrite, and NRF2 mRNA expressions and in the glutathione peroxidase activity in EAC treated with low- and high-dose Cd nanocomplexes. However, the EAC treated with high-dose Cd nanocomplex group showed significant liver and renal toxicity. Conclusion: Cadmium nanocomplex has anticancer effects on EAC induced in mice via its effects on the immune system and redox status as well as pyroptosis and epigenetic instability of the body, while high doses of Cd nanocomplex can cause liver and renal toxicity.

10.
Med Oncol ; 39(10): 150, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35843988

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. TNBC lacks targeted therapy receptors, rendering endocrine and HER2-targeted therapies ineffective. TNBC is typically treated with cytotoxic chemotherapy followed by surgery. Targeting epigenetic modifications could potentially be a new effective TNBC target therapy. The aim of this study is to examine the effects of epigenetic drugs, decitabine as DNA methyltransferase inhibitor (DNMTI) and vorinostat as histone deacetylase inhibitor (HDACI), and the ERß agonist DPN on ERα and ERß re-expressions in the MDA-MB-231 cells as a model of TNBC. METHODS: Using MTT assay, the IC50 of decitabine, vorinostat, and DPN on MDA-MB-231 cells were determined. The effects of all drugs alone or in combinations on MDA-MB-231 cells were evaluated. qRT-PCR was used to determine ERα & ERß gene expression. Caspase-3 activity and the protein expression levels of VEGF, Cyclin D1, and IGF-1 were assessed. RESULTS: Both ERα and ERß mRNA were re-expressed in different high levels in all treated groups, especially in the triple therapy group compared with control. Significantly, the triple drugs therapy showed the lowest levels of VEGF, Cyclin D1, and IGF-1 and the highest level of Caspase-3 activity, indicating a possible antitumor effect of ERß activation through decreasing proliferation and angiogenesis and increasing apoptosis in MDA-MB-231 cells. CONCLUSIONS: The antiproliferative effect of ERß could be retained when co-expressed with Erα using a powerful epigenetic combination of Decitabine and vorinostat with DPN.


Assuntos
Decitabina , Receptor beta de Estrogênio , Nitrilas , Propionatos , Neoplasias de Mama Triplo Negativas , Vorinostat , Humanos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Decitabina/farmacologia , Epigênese Genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Nitrilas/farmacologia , Propionatos/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vorinostat/farmacologia
11.
Redox Rep ; 27(1): 60-69, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35246012

RESUMO

OBJECTIVES: Microbiome-Mitochondria interaction is gaining a significant attention; thus, studying its mechanism emerges as a must to provide restorative lines in managing diseases. The aim is to study the mechanistic effects of ß-Glucan and/or Celastrol in oxazolone-induced ulcerative colitis (UC). METHODS: 75 Wistar rats were allocated into 5 equal groups. Group I: control group. Group II: UC group, Group III: ß-Glucan-treated UC group, Group IV: Celastrol-treated UC group & Group V: mutual treatment group. All groups were subjected to the detection of free fatty acid receptor 2 (FFAR-2) and peroxisome proliferator-activated receptor gamma co-activator1α (PGC-1α) mRNA gene expressions. Citrate synthase (CS) activity, mitochondrial membrane potential (MMP), ATP concentration, reactive oxygen species (ROS) were detected. Trimethylamine N-oxide (TMAO) concentration was measured. RESULTS: After treatment we monitored significant upregulation of FFAR-2 and PGC-1α mRNA expression. Likewise, ATP level and CS activity were significantly increased. On the contrary, there was a significant lessening in ROS and TMAO levels with improvement of MMP. CONCLUSION: Mutual use of ß- Glucan and Celastrol had a greater effect than each alone against UC, which is considered a novel finding highlighting the ameliorative effects of this combined treatment in modulating Microbiome/Mitochondria axis, thus launching promising avenues for UC.


Assuntos
Colite Ulcerativa , beta-Glucanas , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Disbiose/metabolismo , Mitocôndrias/metabolismo , Oxazolona/metabolismo , Oxazolona/farmacologia , Triterpenos Pentacíclicos , Ratos , Ratos Wistar , beta-Glucanas/metabolismo , beta-Glucanas/farmacologia
12.
Vet World ; 14(6): 1677-1681, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34316218

RESUMO

BACKGROUND AND AIM: Avian influenza (AI), which is one of the major respiratory diseases of poultry, and Escherichia coli (E. coli) have caused major economic losses around the world, including in Egypt. Therefore, in this study, we aimed to produce a vaccine from E. coli O157 and AI H5N1 formulated with Montanide ISA70 for the protection of poultry against both diseases. MATERIALS AND METHODS: We divided one hundred 3-week-old chicks into four groups: Group 1 was vaccinated with prepared inactivated AI H5N1formulated with Montanide ISA70, Group 2 was vaccinated with inactivated E. coli formulated with Montanide ISA70, Group 3 was vaccinated with combined E. coli and AI H5N1 formulated with Montanide ISA70, and Group 4 was an unvaccinated control group. We measured the immune response using the HI (hemagglutination inhibition) test, enzyme-linked immunosorbent assay (ELISA), and the challenge test. RESULTS: We found the three vaccines to be safe and sterile during all periods of examination and observation. The HI test showed that Group 1 exhibited specific antibody titers of 2.3 log2, 4.3 log2, 7.5 log2, 7.8 log2, 8 log2, and 8.1 log2 from week 2 to week 7, respectively, post-vaccination. Group 3 exhibited antibody titers of 3.3 log2, 5.8 log2, 7.8 log2, 8 log2, 8.3 log2, and 8.3 log2 from week 2 to week 7, respectively, post-vaccination. The immune response in both groups reached a high titer at week 6. The combined inactivated E. coli and AI H5N1 vaccine generated a higher immune response than the inactivated AI H5N1 vaccine, and a significant difference exists between the two groups. For Groups 2 and 3, the ELISA antibody titer exhibited its lowest value, 1996.5 and 2036.7, respectively, at week 1 post-vaccination; whereas, both groups exhibited the highest titers, 2227.7 (for Group 2) and 2287.3 (for Group 3), in week 3 post-booster. The ELISA for the combined inactivated E. coli and AI H5N1 vaccine had a higher titer than did the inactivated E. coli vaccine, and a significant difference exists between the two groups. Moreover, the protection rate was higher in Group 3, with 100% for E. coli and 90% for the AI H5N1 vaccine. CONCLUSION: Our findings demonstrate that producing a combined vaccine using E. coli and AI H5N1 formulated with Montanide ISA70 is recommended for protection against both diseases.

13.
Pharmaceutics ; 13(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525642

RESUMO

The aim of the current study is to establish a comprehensive experimental design for the screening and optimization of Atorvastatin-loaded nanostructured lipid carriers (AT-NLCs). Initially, combined D-optimal screening design was applied to find the most significant factors affecting AT-NLCs properties. The studied variables included mixtures of solid and liquid lipids, the solid/liquid lipid ratio, surfactant type and concentration, homogenization speed as well as sonication time. Then, the variables homogenization speed (A), the ratio of solid lipid/liquid lipid (B), and concentration of the surfactant (C) were optimized using a central composite design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were chosen as dependent responses. The optimized AT-NLCs demonstrated a nanometric size (83.80 ± 1.13 nm), Polydispersity Index (0.38 ± 0.02), surface charge (-29.65 ± 0.65 mV), and high drug incorporation (93.1 ± 0.04%). Fourier Transform Infrared Spectroscopy (FTIR) analysis showed no chemical interaction between Atorvastatin and the lipid mixture. Differential Scanning Calorimetry (DSC) analysis of the AT-NLCs suggested the transformation of Atorvastatin crystal into an amorphous state. Administration of the optimized AT-NLCs led to a significant reduction (p < 0.001) in serum levels of rats' total cholesterol, triglycerides, and low-density lipoproteins. This change was histologically validated by reducing the relevant steatosis of the liver.

14.
J Biochem Mol Toxicol ; 35(5): e22736, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33512746

RESUMO

BACKGROUND: The field of nanotechnology offers great opportunities for cancer therapy. OBJECTIVE: This study aimed to compare the therapeutic impact of Zn oxide nanoparticles (ZnO NPs) and thymoquinone (TQ) alone or as cotherapy in Ehrlich ascites carcinoma (EAC) induced in mice. MATERIALS AND METHODS: This study was performed on 75 female albino mice divided into Group I: EAC-bearing control group, Group II: EAC treated with TQ, Group III: EAC treated with low-dose ZnO NPs, Group IV: EAC treated with high-dose ZnO NPs, Group V: EAC treated with TQ and low-dose ZnO NPs. All groups were subjected to measurement of cell viability, ascites fluid volume, Bcl2 protein expression by Western blot analysis, cyclooxygenase 2 (COX2) gene expression by a real-time polymerase chain reaction, enzyme-linked immunosorbent assay levels of Beclin 1, interferon γ (INFγ), interleukin 13 (IL-13), and estimation of Zn concentrations in EAC cells and liver homogenate to evaluate its toxicity. RESULTS: Cotherapy has an efficient anticancer effect by enhancing apoptosis and autophagy, resulting in reducing tumor cell viability and ascites fluid volume together with downregulation of Bcl2 protein expression. This cotherapy increases Beclin 1 and INFγ and decreases IL-13. ZnO NPs upregulate COX2 expression, whereas TQ downregulates its expression. High-dose ZnO NPs have more toxic effects on liver enzymes. Using TQ together with ZnO NPs can eliminate ZnO NPs liver toxicity. CONCLUSION: The cotherapy has an efficient anticancer effect by enhancing apoptosis and autophagy. High-dose ZnO NPs have more toxic effects on liver enzymes. Using TQ together with ZnO NPs can eliminate ZnO NP liver toxicity.


Assuntos
Benzoquinonas , Carcinoma de Ehrlich , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Nanopartículas , Proteínas de Neoplasias/biossíntese , Óxido de Zinco , Animais , Benzoquinonas/química , Benzoquinonas/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Feminino , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxido de Zinco/química , Óxido de Zinco/farmacologia
15.
Eur J Gastroenterol Hepatol ; 32(2): 230-236, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243345

RESUMO

INTRODUCTION: There is a growing need for identification of non-endoscopic, non-invasive methods that can accurately predict esophageal varices (EV). Previous studies found an inconclusive correlation between blood ammonia level and the presence and size of EV. AIM: We aimed at assessing the value of serum ammonia as a non-invasive method for early prediction of EV. PATIENT AND METHODS: The study included 204 patients with HCV-related cirrhosis. The selected patients were categorized into two groups: patients with EV and those without, also patients with no or small EV and with large EV group. All patients underwent a complete biochemical workup, ultrasound and upper GI endoscopy. Child-Pugh class, Model of End-Stage Liver Disease (MELD) score and platelet count/splenic diameter ratio, and serum ammonia level. RESULTS: There was a statistical difference between the two groups of patients regarding the following parameters: serum ammonia, international normalized ratio, portal vein diameter, spleen diameter, Child-Pugh class, MELD score, platelet count/splenic diameter ratio, aspartate aminotransferase-to-platelet ratio index, alanine aminotransferase-to-aspartate aminotransferase ratio, Forns index, FIB-4 and King's score. Serum ammonia could predict the presence of EV using a cutoff value of 82 (µmol/L) with a sensitivity of 92.3%, specificity 92%. In addition, a cutoff of 95.5 (µmol/L) could predict large EV with a sensitivity of 92.7% and a specificity of 92.3%. Serum Ammonia in cirrhosis with large EV was 143 ± 39 µmol/L and in cirrhosis with small/without EV was 80.7 ± 9.7 µmol/L (P < 0.0001). Platelet/spleen ratio was 555.9 ± 187.3 in cirrhosis with EV and 694.4 ± 74.2 in cirrhosis without EV (P < 0.0001). Platelet/spleen ratio was 407.7 ± 107.1 in cirrhosis with large EV and 690.4 ± 103.7 in cirrhosis with small/without EV (P < 0.0001). CONCLUSION: Serum ammonia can accurately predict the presence and the size of EV in patients with liver cirrhosis with high sensitivity and specificity.


Assuntos
Amônia , Varizes Esofágicas e Gástricas , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC
16.
Rep Biochem Mol Biol ; 10(3): 362-372, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34981012

RESUMO

BACKGROUND: Epilepsy is one of the most widespread neurological disease worldwide. Status epilepticus (SE) is a life-threatening neurologic disorder. Neuroprotective approaches are increasingly to discover a promising therapy to manage epileptic disorders. This study aimed to assess the impact of berberine on some epigenetic, transcription regulation & inflammatory biomarkers in a mice model of epilepsy. METHODS: This work was performed on; Group I: (control), Group II: berberine-treated control,Group III: epilepsy group, Group IV: berberine-treated epilepsy. Groups were subjected to assessment of Tumor growth factor-1ß (TGF-1ß), hypoxia inducible factor-1α (HIF-1α), brain derived neurotrophic factor (BDNF) levels, histone deacetylase (HDAC) activity & neuronal restrictive silencing factor (NRSF) gene expression. RESULTS: Study showed significant increase in levels of HIF-1α, TGF-1ß, HDAC activity & NRSF gene expression in epilepsy group & decrease in these levels in berberine treated epilepsy group. Significant decrease in BDNF levels in epilepsy & elevation in them in berberine treated epilepsy group. CONCLUSION: Our study showed the anti-epileptic impact of berberine via its regulatory effect on some epigenetic, transcription factors & inflammatory biomarkers in a mice model of epilepsy.

17.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e978-e985, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35048659

RESUMO

BACKGROUND: A systemic inflammatory response syndrome (SIRS) is linked to red cell distribution width (RCDW), which produces pro-inflammatory signals that act directly on hematopoietic stem cells in the bone marrow. This stimulation may cause alterations in the membrane of red blood cells (RBCs), as assessed by RCDW, which have been linked to increased morbidity and death in a number of systemic disorders. AIM: This study aims to evaluate RCDW as a predictor of outcome in hospitalized cirrhotic patients. METHODS: This prospective cross-sectional study was conducted on 1000 patients. The outcome was assessed by days of hospitalization; mortality in hospitalized patients or during short-term follow-up (3 months) and rehospitalization during follow-up of 6 months. RESULTS: Male represented 69.6%. Mean age was 57.67 ± 13.07 years old. Baseline co-morbidities were recorded as the presence of diabetes mellitus (200 patients) and hypertension (400 patients). Hepatitis C virus was the commonest etiology of the diseased liver (90%). Child-Pugh classes A, B and C of studied patients represented (21.2%, 38.8% and 40%). The survived patients during follow-up represented 63.3%. Area under the curve for RCDW was 0.923 (95% CI, 0.904-0.943), 0.910 for C-reactive protein (95% CI, 0.890-0.930), 0.904 for Hb (95% CI, 0.883-0.925) and 0.903 for platelets (95% CI, 0.882-0.924). RCDW cutoff point at 21.35 for predicting survival had sensitivity 93%, specificity 91%, accuracy 92%, positive predictive value 85 and negative predictive value 96. Regression analysis revealed a significant positive association between both RCDW and white blood cells with mortality. CONCLUSION: RCDW could provide useful information for predicting the length of hospitalization and survival in hospitalized cirrhotic patients.


Assuntos
Índices de Eritrócitos , Síndrome de Resposta Inflamatória Sistêmica , Adulto , Idoso , Estudos Transversais , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Síndrome de Resposta Inflamatória Sistêmica/etiologia
18.
Clin Exp Hepatol ; 7(4): 370-376, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35402715

RESUMO

Aim of the study: Despite achieving a high cure rate of chronic hepatitis C nowadays, treatment failure remains a major concern and host genetic polymorphism could have a possible relation. The aim was to evaluate the role of chemokine receptor CXCR6 gene polymorphism in treatment response to direct acting antivirals (DAAs) in chronic hepatitis C virus (HCV) patients. Material and methods: We investigated the chemokine receptor CXCR6 gene single nucleotide polymorphism rs2234358 in three groups. Responder and non-responder groups (each comprising 50 naïve patients) and a control group of 50 apparently healthy individuals were studied. Results: Genotype distribution revealed a significant difference (p = 0.037) between non-responders and the other 2 groups. Both control and responder groups showed allelic frequencies of 20% having the wild allele G and 80% having the variant allele T, while in the non-responder group 39% had G and 61% had the T alleles. Genotype GG was associated with significant increased risk of not responding to treatment by 4.25 times as compared with TT genotype (p = 0.019) and the G allele was associated with highly significant risk of not responding to treatment by 2.56 times compared with the T allele (p = 0.003). Conclusions: CXCR6 gene (rs2234358) polymorphism could have a potential role in the virological treatment response with a protective effect of the T allele. This could explain the higher treatment success rate of Egyptian HCV patients.

19.
Clin Exp Hepatol ; 6(3): 263-269, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33145433

RESUMO

AIM OF THE STUDY: We aimed to evaluate the association of microRNA-499 rs3746444 polymorphism and biliary atresia (BA) risk and its correlation with clinic-pathologic features of BA. MATERIAL AND METHODS: This study was performed on 300 Egyptian children (100 BA cases, 100 cases with cholestatic liver diseases other than BA and 100 healthy controls). Routine laboratory investigations, clinical examination and abdominal ultrasound were done. All infants were genotyped for miR-499 single nucleotide polymorphisms (SNPs) (rs3746444 A>G) by real-time polymerase chain reaction (PCR) fluorescence detection on a Rotor Gene Real Time PCR System (QIAGEN, GmbH) using fluorescent labeled probes. RESULTS: The AG genotype was the most prevalent genotype of miR-499 rs3746444 among the studied groups. A significantly higher frequency of the rs3746444 G allele was found in the BA cases than the other groups (odds ratio = 1.62). This polymorphism was also correlated with the degree of fibrosis in BA cases (p < 0.05). The miR-499 rs3746444 polymorphism (GG genotype) was significantly associated with severe form of BA and bad prognosis after the Kasai operation (p < 0.05). miR-499 rs3746444 polymorphism had no effect on the clinic-pathological features or the liver function status in the non-BA group. CONCLUSIONS: There is an association between the miR-499 SNP genotypes and the occurrence of BA. The variant allele G is the predominant allele in the BA group and is associated with severe liver inflammation and bad prognosis after the Kasai operation.

20.
Nanotechnology ; 31(30): 305706, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32235044

RESUMO

Novel supported inorganic metal nano-complexes of Ag(I) and Co(II) derived from 4-amino-N-(4-methylpyrimidin-2-yl) benzene sulfonamide (SulMer) were synthesized using olive leaf extract as a reducing agent with grinding and microwave methods. The prepared samples were denoted as Comp1-6. The surface morphologies of the synthesized nanomaterials were analyzed using C, H, N, S analysis, Fourier-transform infrared spectroscopy, UV- visible spectroscopy, proton and carbon nuclear magnetic resonance, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and x-ray powder diffraction (XRD) analysis. The data revealed that all the synthesized complexes exhibited a 1:1 metal-to-ligand ratio with a coordination number of 4 or 6. The mean particle size of the nanomaterial samples was 25-35 nm. The XRD patterns indicated a crystalline nature for the complexes. The supported inorganic metal nano-complexes displayed good activity in the adsorptive removal of Direct Red 81 (DR-81) from aqueous solutions. In addition, the effect of the supported metal nano-complexes on the immune system was studied as well as how these anti-inflammatory compounds could be used to treat many autoimmune diseases, most notably rheumatoid arthritis. An experimental model for arthritis can be induced using complete Freund's adjuvant. It was shown that the supported complex offers several advantages such stability, eco-friendliness, simple experimental conditions, short reaction times, and easy work- up.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Cobalto/administração & dosagem , Adjuvante de Freund/efeitos adversos , Prata/administração & dosagem , Adsorção , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/induzido quimicamente , Compostos Azo/química , Cobalto/química , Cobalto/uso terapêutico , Modelos Animais de Doenças , Feminino , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Olea/química , Tamanho da Partícula , Folhas de Planta/química , Ratos , Prata/química , Prata/uso terapêutico
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