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1.
BMC Gastroenterol ; 24(1): 337, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350070

RESUMEN

BACKGROUND: Proteoglycans are important tumor microenvironment extracellular matrix components. The regulation of key proteoglycans, such as decorin (DCN), by miRNAs has drawn attention since they have surfaced as novel therapeutic targets in cancer. Accordingly, this study aimed at identifying the impact of miR-181a in liver cancer and its regulatory role on the extracellular matrix proteoglycan, DCN, and hence on downstream oncogenes and tumor suppressor genes. RESULTS: DCN was under-expressed in 22 cirrhotic and HCC liver tissues compared to that in 11 healthy tissues of liver transplantation donors. Conversely, miR-181a was over-expressed in HCC liver tissues compared to that in healthy liver tissues. In silico analysis predicted that DCN 3'UTR harbors two high-score oncomiR-181a binding regions. This was validated by pmiRGLO luciferase reporter assay. Ectopic miR-181a expression into HuH-7 cells repressed the transcript and protein levels of DCN as assessed fluorometrically and by western blotting. DCN siRNAs showed similar results to miR-181a, where they both enhanced the cellular viability, proliferation, and clonogenicity. They also increased Myc and E2F and decreased p53 and Rb signaling as assessed using reporter vectors harboring p53, Rb, Myc, and E2F response elements. Our findings demonstrated that miR-181a directly downregulated the expression of its direct downstream target DCN, which in turn affected downstream targets related to cellular proliferation and apoptosis. CONCLUSION: To our knowledge, this is the first study to unveil the direct targeting of DCN by oncomiR-181a. We also highlighted that miR-181a affects targets related to cellular proliferation in HCC which may be partly mediated through inhibition of DCN transcription. Thus, miR-181a could be a promising biomarker for the early detection and monitoring of liver cancer progression. This would pave the way for the future targeting of the oncomiR-181a as a therapeutic approach in liver cancer, where miR-181a-based therapy approach could be potentially combined with chemotherapy and immunotherapy for the management of liver cancer.


Asunto(s)
Carcinogénesis , Carcinoma Hepatocelular , Decorina , Neoplasias Hepáticas , MicroARNs , Decorina/genética , Decorina/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Carcinogénesis/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Persona de Mediana Edad , Femenino , Regulación hacia Abajo
2.
J Genet Eng Biotechnol ; 22(3): 100395, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39179318

RESUMEN

Prostate cancer (PCa) is a prevalent form of malignancy in males and is a significant contributor to cancer-related mortality worldwide. Because of this, studying the molecular processes of PCa cell growth and death is crucial. Hence, it is imperative to conduct further research on the regulatory mechanism underlying the progression of PCa to enhance our comprehension and identify innovative therapeutic targets. The present study investigates an experimental approach that utilizes cost-effective and environmentally sustainable plant extracts sourced from Egypt, namely ginger, chamomile, and green tea, which have been solubilized in dimethyl sulfoxide (DMSO), then characterized by using different analytical means and techniques, such as HPLC and GC-MS. The present study employed MTT assay, ELISA, and qRT-PCR techniques to assess the possible impact of the investigated extracts on PCa in PC-3 cells. The findings indicate that ginger exhibited a noteworthy cytotoxic impact on PC-3. Remarkably, the treatment of PCa cells with ginger significantly increased relative lactate dehydrogenase (LDH) production compared to those treated with chamomile and green tea extracts. Autophagy may play a crucial role in the context of chemotherapy. Modifying autophagy through its induction or inhibition is a promising and innovative approach to controlcancer progression. Accordingly, it was found that ginger extract affects protein expression levels of autophagy markers LC3B, ATg12, and pro-apoptotic signaling, including the Caspase-3 signaling pathway. The ELISA findings revealed a significant rise in the average levels of IL-1ß and IL-8 after a 12-hour interval. To conclude, it can be inferred that ginger extract possesses the capability to control the production of inflammatory cytokines. Alternatively, utilizing herbal remedies containing ginger as a viable and secure means of treating PCa as an anticancer agent is possible.

3.
Eur J Drug Metab Pharmacokinet ; 49(5): 583-594, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38914798

RESUMEN

BACKGROUND AND OBJECTIVES: Both AW-9A (coumarin derivative) and WES-1 (sulfonamide derivative) were designed and synthesized as potential selective carbonic anhydrase inhibitors and were tested for anticancer activity. This study was undertaken to investigate their potential inhibitory effects on the major human cytochrome P450 (CYP) drug-metabolizing enzymes. METHODS: Specific CYP probe substrates and validated analytical methods were used to measure the activity of the tested CYP enzymes. Furthermore, in silico simulations were conducted to understand how AW-9A and WES-1 bind to CYP2A6 at a molecular level. Molecular docking experiments were performed using the high-resolution X-ray structure, Protein Data Bank (PDB) ID: 2FDV for CYP2A6. RESULTS: CYP2E1-catalyzed chlorzoxazone-6'-hydroxylation was strongly inhibited by AW-9A and WES-1 with IC50 values of 0.084 µM and 0.101 µM, respectively. CYP2A6-catalyzed coumarin-7'-hydroxylation was moderately inhibited by AW-9A (IC50 = 4.2 µM). CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes were weakly or negligibly inhibited by both agents. Docking studies suggest elevated potential to block the catalytic activity of CYP2A6. CONCLUSIONS: These findings point to the feasibility of utilizing these agents as promising chemopreventive agents (owing to inhibition of CYP2E1), and AW-9A as a smoking cessation aid (owing to inhibition of CYP2A6). Additional in-vivo studies should be conducted to examine the impact of CYP2A6 and CYP2E1 inhibition on drug interactions with probe substrates of these enzymes.


Asunto(s)
Inhibidores de Anhidrasa Carbónica , Cumarinas , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450 , Simulación del Acoplamiento Molecular , Humanos , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Cumarinas/farmacología , Cumarinas/química , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Sulfonamidas/farmacología , Sulfonamidas/química , Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2A6/antagonistas & inhibidores
4.
Surgeon ; 22(3): 133-137, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631982

RESUMEN

BACKGROUND: As waiting lists for elective surgery grow, there seems to be a disconnect between the public's expectations on the amount of time surgeons spend operating compared with reality. On average, a surgeon in the NHS spends one day a week performing elective surgery. We aimed to investigate the public's perception on the amount of time surgeons spend performing elective surgery and what they would desire. METHODS: Members of the public in the UK were approached randomly either on-line or in-person to complete an anonymised 6-question survey. The questionnaire included demographic details, surgical history, occupational experience in the healthcare sector, the number of days a week they believe and wish for surgeons to be performing elective surgery. RESULTS: 252 members of the public responded to the survey (150 females, 102 males). 38.5% have experience working in the healthcare sector and 58.5% have had surgery in the past. 83.7% believe surgeons spend at least 3 days a week performing elective surgery [3-4 days (43.2%), 5-7 days (40.5%)]. 45.7% of respondents want their surgeon to operate between 5 and 7 days per week. CONCLUSION: The public appears to overestimate the amount of time that surgeons spend performing elective surgery and have unrealistic expectations of how much they want their surgeons to operate.


Asunto(s)
Procedimientos Quirúrgicos Electivos , Cirujanos , Humanos , Femenino , Masculino , Cirujanos/psicología , Cirujanos/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Reino Unido , Factores de Tiempo , Opinión Pública , Adulto Joven , Anciano , Adolescente
5.
Heliyon ; 10(7): e29128, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38623208

RESUMEN

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

6.
Heliyon ; 10(3): e25607, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38356540

RESUMEN

Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.

7.
J Egypt Natl Canc Inst ; 36(1): 2, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38246972

RESUMEN

BACKGROUND: Metastatic tumors account for 80% of all lung tumors in children. Wilms tumour and osteosarcoma are the most tumors of childhood that produce lung metastases. The aim of the current study is to assess the prognostic factors of pulmonary metastatectomy in pediatric solid tumours as age, number, size, site,laterality, resectability of pulmonary nodules, and number of Thoracotomies. Calculate overall survival among patients who underwent pulmonary metastatectomy. METHODS: It is a retrospective study including all pediatric patients with metastatic solid tumors to lungs treated at pediatric oncology department, National Cancer Institute, Cairo University from 2008 to 2014. Fifty-five patients were included, 43 (78.2℅) patients of them had Osteosarcoma. RESULTS: Thirty (54.5℅)patients were male. The mean age was 15 years ranging from (4.5- 23) years. The site of primary disease was at lower limbs in 43 (78.2%) patients. All patients underwent complete surgical resection of the primary disease with negative margin, 22(51.1%) of the osteosarcoma patients did amputation with tumor necrosis less than 90%. All patients received chemotherapy and only 9 received radiation therapy. The patients were classified into four groups according to time of diagnosis of pulmonary metastasis: at time of diagnosis in 13 (21.8%) patients, within treatment in 16 (30.9%) patients, within first year follow up in 18 (32.7%) patients and detected late in 8 (14.5%) patients. Bilateral lung metastasis diagnosed by CT chest were detected in 42 (76.4%) patients. Size of metastatic nodules was ranging from (0.5 to 10 cm) with mean 3.4 cm. Number of metastatic nodules was ranging from (1 to 28) median 4.Metastatic complications were detected in 19 patients. 5-year OS was 74.8% in the study group, and 68% in osteosarcoma patients. Effect of prognostic factors as sex, time of respectability, laterality, tumor necrosis of the 1ry disease, Timing of lung metastasis, size and site of the primary, Surgical approach of metastatectomy, postoperative complications on overall survival of the studied patients was done with significant P-value of tumor necrosis of the 1ry disease and Timing of lung metastasis 0.017, 0.001 respectively. CONCLUSION: Resection of pulmonary metastases of pediatric solid tumours is a safe and effective treatment that offers better survival.


Asunto(s)
Neoplasias Óseas , Neoplasias Renales , Neoplasias Pulmonares , Osteosarcoma , Estados Unidos , Humanos , Masculino , Niño , Adolescente , Femenino , Egipto/epidemiología , National Cancer Institute (U.S.) , Pronóstico , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Osteosarcoma/cirugía , Neoplasias Óseas/cirugía , Pulmón , Necrosis
8.
Microsurgery ; 44(1): e31105, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37675648

RESUMEN

BACKGROUND: The selection of reliable recipient vessels is essential for successful free tissue transfer. The use of internal mammary intercostal perforators (IMAPs), instead of the internal mammary vessels as the recipient vessels, has been described in breast reconstruction. Debates exist regarding the reliability of these perforators as recipient vessels because of their variability in location and caliber. The aim of this paper was to conduct a systematic literature review and meta-analysis to determine the reliability of the IMAPs as recipient vessels. METHODS: A systematic literature review was performed on the "PubMed," "Medline," "Ovid," and "Cochrane library" databases for articles published from January 1990 to March 2021. Exclusion criteria were non-English studies, reports with case number less than 5, cadaveric or animal studies, and studies with incomplete postoperative outcomes. The reliability of using IMAPs for breast reconstruction was determined by assessing the reported rates of partial or complete flap failure and other complications (fat necrosis, skin necrosis, and requirement for revision surgery). RESULTS: Three hundred and sixteen cases in 13 studies were included for further analysis with more than 85% of the IMAPs suitable for anastomosis being located in the second and third intercostal spaces. Partial or total flap failure was reported in three of 316 patients (0.95%). The rate of other complications such as fat necrosis, skin necrosis, and requirement for revision surgery were all less than 5%. CONCLUSION: With deliberate preoperative planning, delicate perioperative manipulation, and meticulous microvascular anastomosis, the internal mammary perforators can be used as reliable recipient vessels in microvascular breast reconstruction.


Asunto(s)
Necrosis Grasa , Mamoplastia , Arterias Mamarias , Humanos , Colgajos Quirúrgicos/irrigación sanguínea , Necrosis Grasa/etiología , Reproducibilidad de los Resultados , Arterias Mamarias/cirugía , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/etiología
9.
Surgeon ; 22(1): 1-5, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37793946

RESUMEN

BACKGROUND: Worldwide, there is significant variation in the amount of time surgeons spend performing elective surgery. The degree of variation is unknown. The aim of this study was to assess the variation in amount of time that surgeons spend operating worldwide. METHODS: An anonymised electronic survey was sent via email to members of The Upper Gastrointestinal Surgeons (TUGS) and shared via social media. The questionnaire consisted of demographic details (age, gender, country of practice), scope of practice (full time/less than full time; private/public sector), experience and average number of days the surgeon spends performing elective surgery. RESULTS: A total of 225 predominantly general/upper GI surgeons from 47 countries responded. Worldwide, the median number of days that surgeons spend performing elective surgery is 2 days a week. There was significant variation across countries/continents: UK 1 day; North America 2.5 days; Europe 3 days; Asia 2 days; Africa 2 days; South America 1 day; Oceania 1 day (p < 0.0001). All surgeons worldwide preferred to spend 3 days a week performing elective surgery except UK surgeons who desired 2 days a week. CONCLUSION: There is significant variation in the amount of time that surgeons spend performing elective surgery worldwide. Results of this study could inform public expectations and trainee surgeons on ideal opportunities for training. Reasons for the wide variation could be explored.


Asunto(s)
Cirujanos , Humanos , Cirujanos/educación , Europa (Continente) , Procedimientos Quirúrgicos Electivos , Encuestas y Cuestionarios
10.
J Asthma ; 61(7): 677-684, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38153520

RESUMEN

OBJECTIVE: We aimed to compare the effectiveness of three distinct counseling methods to determine the most effective approach. METHODS: In this prospective cohort study with a two-month follow-up, A group of non-smoking adults, aged 19-60 years, were randomly collected at outpatients clinic with prior asthma diagnosis, based on the forced expiratory volume in one seconds to forced vital capacity ratio (FEV1/FVC) and the guidelines outlined by the Global Initiative for Asthma (GINA), At the baseline assessment, all patients, underwent FEV1/FVC measurements, asthma symptom evaluations using Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and GINA symptoms control assessment questionnaire, and assessment of pressurized metered-dose inhaler (pMDI) usage. The patients were divided into three groups, each assigned a distinct counseling strategy: traditional verbal counseling, advanced counseling utilizing the Asthma smartphone-application, and a combination of advanced-verbal counseling. We conducted a two-month monitoring period for all three groups. RESULTS: Significant differences (p < .001) were observed among the three counseling groups in ACT, FEV1/FVC ratio, and GINA symptoms control assessment scores from the first month to the second month visit. Regarding ACQ, the study unveiled a noteworthy disparity in ACQ scores during the second week, with a significant difference (p = .025) observed between the verbal and advanced-verbal counseling groups. Similarly, a significant difference (p = .016) was noted between the advanced counseling group and the advanced-verbal counseling groups. CONCLUSION: The study findings indicate that the combining advanced-verbal counseling by incorporating the Asthma smartphone-application alongside traditional verbal counseling is a more effective approach for improving asthma control in adults.


Asunto(s)
Asma , Consejo , Humanos , Asma/fisiopatología , Asma/tratamiento farmacológico , Adulto , Masculino , Femenino , Persona de Mediana Edad , Consejo/métodos , Estudios Prospectivos , Adulto Joven , Volumen Espiratorio Forzado , Capacidad Vital , Inhaladores de Dosis Medida , Teléfono Inteligente , Aplicaciones Móviles
12.
World J Surg ; 47(6): 1348-1357, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36811667

RESUMEN

BACKGROUND: The ward round is an integral part of everyday surgical practice. It is a complex clinical activity that requires both sound clinical management and communication skills. This study reports the results of a consensus-building exercise on the common aspects of the general surgical ward rounds. METHODS: The consensus-building committee involving a range of stakeholders from 16 United Kingdom (UK) National Health Service trusts took part in this consensus exercise. The members discussed and suggested a series of statements concerning surgical ward round. An agreement of ≥ 70% among members was regarded as a consensus. RESULTS: Thirty-two members voted on 60 statements. There was a consensus on fifty-nine statements after the first round of voting, and one statement was modified before it reached consensus in the second round. The statements covered nine sections: a preparation phase, team allocation, multidisciplinary approach to the ward round, structure of the round, teaching considerations, confidentiality and privacy, documentation, post-round arrangements, and weekend round. There was a consensus on spending time to prepare for the round, a consultant-led round, involvement of the nursing staff, an MDT round at the beginning and end of the week, a minimum of 5 min allocated to each patient, utilisation of a round checklist, afternoon virtual round, and a clear handover and plan for the weekend. CONCLUSION: The consensus committee achieved agreement on several aspects concerning the surgical ward rounds in the UK NHS. This should help improve the care of surgical patients in the UK.


Asunto(s)
Medicina Estatal , Humanos , Consenso , Técnica Delphi , Reino Unido
13.
Br J Neurosurg ; 37(6): 1699-1703, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32959706

RESUMEN

We present a rare case of giant perivascular space in mesencephalo-thalamic region causing hydrocephalus. The patient presented insidiously over 6 months. However, the patient suddenly deteriorated in the hospital with visual symptoms, increasing headache and papilloedema, prompting urgent VP shunt and biopsy. Patient's symptoms resolved completely after decompression and he continues to remain symptom free. This patient is only the second described case of giant perivascular space with sudden deterioration of symptoms. This case report is intended to highlight this rare presentation of this cyst which can potentially suggest a more aggressive underlying lesion and prompt a biopsy which can be risky, given the proximity to perforators and normal structures, which is otherwise not necessary.


Asunto(s)
Quistes , Hidrocefalia , Masculino , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Quistes/complicaciones , Cefalea/complicaciones , Imagen por Resonancia Magnética
14.
J Reconstr Microsurg ; 39(7): 540-548, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36577496

RESUMEN

BACKGROUND: One of the most challenging yet common areas in reconstructive surgery is the closure of defects in the lower leg. Surgeons can choose from several reconstructive options including local and free flaps. The aim of this study was to understand the reconstructive strategy for lower leg defects of different microsurgeons around the world by harnessing the power of social media and online questionnaires. METHODS: A case of a patient with an exposed plate over distal tibial fracture was presented via an online questionnaire distributed on various social media platforms. A total of 369 international microsurgeons replied with their preferred treatment choice. The data were analyzed according to geographic area, microsurgical training, seniority, and subspecialty. RESULTS: Among all the respondents (n = 369), 64% would have opted for a free flap reconstruction, while the remaining 36% would have opted for a local/pedicle flap. In the group that would have opted for a free flap, 63% would reconstruct the defect using a free fasciocutaneous flap, while the remaining 37% would have used a free muscle flap. In the local flap group, 60% would have used a local perforator while 30% would have chosen a conventional local flap. While North American and European microsurgeons had a clear preference toward free flaps, Asian, Middle Eastern, African, and South American surgeons were evenly divided between local and free flaps. CONCLUSION: In this study, we provide a current global overview of the reconstructive strategies for a lower limb with skin defect and bone or prosthesis exposure. We hope that this will be able to help global microsurgeons and patients worldwide.


Asunto(s)
Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Humanos , Colgajos Tisulares Libres/cirugía , Tibia/cirugía , Pierna/cirugía , Encuestas y Cuestionarios , Colgajo Perforante/cirugía
15.
J Clin Densitom ; 26(1): 61-82, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36535857

RESUMEN

BACKGROUND: In the development of rheumatoid arthritis, the cytokine interleukin-6 plays a role. An interleukin-6 cytokine-specific monoclonal antibody called olokizumab directly targets this cytokine. OKZ effectiveness and safety are being evaluated through this meta-analysis. METHOD: I looked up every published randomized controlled study on Clinicaltrials.gov, Scopus, Web of Science, Cochrane, and PubMed. I conducted the study using both the Mantel-Haenszel and inverse variance approaches. I evaluated bias in the included studies using the risk of bias tool 2. RESULTS: In this meta-analysis, five trials totalling 2227 participants, were examined. In contrast to the placebo group, the olokizumab group had a significantly higher incidence of American College of Rheumatology 20; RR = 1.83, 95% CI [1.69, 1.99], P < 0.00001. Regarding Health Assessment Questionnaire-Disability Index improvement, olokizumab significantly outperformed the placebo group; MD = -0.28, 95% CI [-0.32, -0.24], P < 0.00001. The incidence of treatment-emergent adverse events was significantly higher in the olokizumab group than in the placebo group; RR = 1.10, 95% CI [1.04, 1.17], P = 0.0006. Furthermore, the incidence of treatment-emergent serious adverse events did not differ significantly between the olokizumab group and the placebo group; RR = 0.85, 95% CI [0.60, 1.20], P = 0.35. CONCLUSION: In patients with rheumatoid arthritis, olokizumab combined methotrexate is well tolerated and more effective than placebo plus methotrexate.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Humanos , Metotrexato/uso terapéutico , Antirreumáticos/efectos adversos , Interleucina-6 , Ensayos Clínicos Controlados Aleatorios como Asunto , Artritis Reumatoide/tratamiento farmacológico , Citocinas , Resultado del Tratamiento
16.
Front Vet Sci ; 9: 1042640, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36524230

RESUMEN

The study objective was to evaluate Allium sativum's potential and Nigella Sativa's combination's potential to reduce aluminum toxicity and return to the normal state. In the present study, a hundred albino rats were randomly divided into five equal groups. The first group was used as a control group; the other four groups were exposed to aluminum 1,600 ppm. The second exposed to aluminum only; the third and fourth groups were treated with Allium sativum 5% and Nigella sativa 5%, respectively, while the fifth group was treated with a mix of Allium sativum 2.5% and Nigella sativa 2.5% for 8th weeks. After 8 weeks, the aluminum administration was stopped, and the second group was divided into three groups. The groups were treated with Allium sativum 5% and Nigella sativa 5%, and a mix of Allium sativum 2.5% and Nigella sativa 2.5%, respectively. The first group was the control group (continued from the first experiment). Garlic and Nigella sativa were crushed and added to feed while receiving aluminum chloride daily at a dose of 1.6 ml/l was added to the drinking water. Histopathological changes in the liver, kidney, and testes were investigated after 8 and 16 weeks, and blood samples were collected after 4, 8, and 16 weeks for biochemical blood parameters. The results showed that the histopathological examination of the liver, kidney, and testes showed signs of congestion in blood vessels after aluminum exposure. Meanwhile, the treatment with Allium sativum or Nigella sativum or the mixture between them had positive effects on evading the harmful effects of aluminum in the liver, Kidney, and testes tissues. In addition, there were protective effects for Allium sativum and Nigella sativa against aluminum on serum creatinine, urea, ALT, and AST concentrations. The present study concluded that supplementation with Allium sativum or Nigella sativa or their combination could reduce aluminum toxicity and return the liver, kidney, and testes to normal.

17.
Front Vet Sci ; 9: 935634, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36268048

RESUMEN

The present study aims to evaluate the effects of prepartum maternal supplementation of Capsicum oleoresin (CAP) on colostrum quality and growth performance in newborn buffalo calves. Twelve multiparous buffaloes were randomly assigned to two groups starting from 4 weeks prepartum: the control group with a basal diet (CON) and the treatment group with a basal diet supplemented with 20 mg CAP/kg dry matter (CAP20). After birth, all calves were weighed and received colostrum from their respective dam directly within 2 h. After that, calves received pasteurized milk and starter feed till 56 days of age. The results showed that CAP increased lactose (P < 0.05) in colostrum, and it tended to increase monounsaturated fatty acids; however, it decreased colostrum urea nitrogen (P < 0.10). CAP did not affect colostrum yield and immunoglobulin G and M concentrations. The weekly starter intake was not affected by maternal CAP supplementation during the first 6 weeks of life. There was an increasing tendency in weekly starter intake from weeks 7 and 8 (P < 0.10) in CAP20 compared with CON. At 7 days of age, calves in CAP20 had higher immunoglobulin G (P < 0.05) and a decreased tendency in calves' serum glucose compared with CON. Additionally, maternal CAP supplementation increased calves' serum ß-hydroxybutyric acid (P < 0.05) and tended to increase total protein (P < 0.10), while decreased non-esterified fatty acids (P < 0.05) at 56 days of age. Calves in CAP20 had higher final withers height, final heart girth, average withers height, and average heart girth than the CON (P < 0.05). These results suggest that maternal CAP supplementation could improve colostrum quality and positively affect the performance of buffalo calves.

18.
Front Microbiol ; 13: 1005818, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36225375

RESUMEN

This study aimed to determine the effect of capsicum oleoresin (CAP) on rumen fermentation and microbial abundance under different temperature and dietary conditions in vitro. The experimental design was arranged in a 2 × 2 × 3 factorial format together with two temperatures (normal: 39°C; hyperthermal: 42°C), two forage/concentrate ratios (30:70; 70:30), and two CAP concentrations in the incubation fluid at 20 and 200 mg/L with a control group. Regarding the fermentation characteristics, high temperature reduced short-chain fatty acids (SCFA) production except for molar percentages of butyrate while increasing acetate-to-propionate ratio and ammonia concentration. The diets increased total SCFA, propionate, and ammonia concentrations while decreasing acetate percentage and acetate-to-propionate ratio. CAP reduced acetate percentage and acetate-to-propionate ratio. Under hyperthermal condition, CAP could reduce acetate percentage and increase acetate-to-propionate ratio, lessening the negative effect of high heat on SCFA. Hyperthermal condition and diet altered the relative abundance of microbial abundance in cellulose-degrading bacteria. CAP showed little effect on the microbial abundance which only increased Butyrivibrio fibrisolvens. Thus, CAP could improve rumen fermentation under different conditions, with plasticity in response to the ramp of different temperature and dietary conditions, although hardly affecting rumen microbial abundance.

19.
Neurotoxicology ; 92: 77-90, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35843304

RESUMEN

The cognitive and behavioral decline observed in cancer survivors who underwent doxorubicin (DOX)-based treatment raises the need for therapeutic interventions to counteract these complications. Galangin (GAL) is a flavonoid-based phytochemical with pronounced protective effects in various neurological disorders. However, its impact on DOX-provoked neurotoxicity has not been clarified. Hence, the current investigation aimed to explore the ability of GAL to ameliorate DOX-provoked chemo-brain in rats. DOX (2 mg/kg, once/week, i.p.) and GAL (50 mg/kg, 5 times/week., via gavage) were administered for four successive weeks. The MWM and EPM tests were used to evaluate memory disruption and anxiety-like behavior, respectively. Meanwhile, targeted biochemical markers and molecular signals were examined by the aid of ELISA, Western blotting, and immune-histochemistry. In contrast to DOX-impaired rats, GAL effectively preserved hippocampal neurons, improved cognitive/behavioral functions, and enhanced the expression of the cell repair/growth index, BDNF. The antioxidant feature of GAL was confirmed by the amelioration of MDA, NO and NOX-1, along with restoring the Nrf-2/HO-1/GSH cue. In addition, GAL displayed marked anti-inflammatory properties as verified by the suppression of the HMGB1/TLR4 nexus and p-NF-κB p65 to inhibit TNF-α, IL-6, IL-1ß, and iNOS. This inhibitory impact extended to entail astrocyte activation, as evidenced by the diminution of GFAP. These beneficial effects were associated with a notable reduction in p-p38MAPK, p-JNK1/2, and p-ERK1/2, as well as the necroptosis cascade p-RIPK1/p-RIPK3/p-MLKL. Together, these pleiotropic protective impacts advocate the concurrent use of GAL as an adjuvant agent for managing DOX-driven neurodegeneration and cognitive/behavioral deficits. DATA AVAILABILITY: The authors confirm that all relevant data are included in the supplementary materials.


Asunto(s)
Disfunción Cognitiva , Doxorrubicina , Flavonoides , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Biomarcadores/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Doxorrubicina/toxicidad , Flavonoides/farmacología , Flavonoides/uso terapéutico , Factor de Transcripción de la Proteína de Unión a GA/metabolismo , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacología , Proteína HMGB1/uso terapéutico , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Proteínas Quinasas , Ratas , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
20.
Int J Surg Case Rep ; 97: 107385, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35868132

RESUMEN

INTRODUCTION AND IMPORTANCE: Dentigerous cysts are benign odontogenic cysts of developmental origin. Enucleation and marsupialization are still considered the blueprint of cystic lesion treatment. CASE PRESENTATION: A 23-year-old male patient presented complaining of a minimal swelling in his upper jaw with slight tenderness in his upper anterior teeth. Cone Beam Computed Tomography (CBCT) on the maxilla was requested. The cystic lesion was found to be minimally expansile with intact cortical plates of the maxilla in the affected area. The CBCT was used to fabricate a cutting guide to determine the exact location of the bony window to fully access the lesion. Root canal treatment was done for the affected non-vital teeth. The cuts were done using a piezo-electric device. Complete enucleation was done for the lesion followed by fixation of the cortical bone lid using micro-plates and screws. The case was followed up after 6 months for new bone deposition using CBCT and 1 week, 1 month, and 6 months postoperatively for postoperative pain using the Visual Analogue Scale (VAS). CLINICAL DISCUSSION: Piezo-electric surgery was used due to the selective cutting merit to cut through bone while preserving the cystic lining intact. Lid surgery aims to maximize the volume of bone deposited in place of the defect by converting the cavity of the cystic lesion into a contained defect. CONCLUSION: Guided lid surgery using a piezo-electric device could be a useful technique for cystic enucleation regarding the new bone formation and pain level.

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