Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Янв. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Язык: Английский

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Combination Therapy as a Promising Way to Fight Oral Cancer

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1653 - 1653

Опубликована: Июнь 4, 2023

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, radiation therapy, alone or in combination, are associated significant side effects. Currently, combination therapy has become the standard practice for of locally advanced oral cancer, emerging an effective approach improving outcomes. In this review, we present in-depth analysis current advancements therapies cancer. The review explores therapeutic options highlights limitations monotherapy approaches. It then focuses on combinatorial approaches target microtubules, well various signaling pathway components implicated progression, namely, DNA repair players, epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, immune checkpoint proteins. discusses rationale behind combining different agents examines preclinical clinical evidence supporting effectiveness these combinations, emphasizing their ability enhance response overcome drug resistance. Challenges discussed, including potential toxicity need personalized A future perspective also provided highlight existing challenges possible resolutions toward translation therapies.

Язык: Английский

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Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives

Phytomedicine, Год журнала: 2023, Номер 121, С. 155100 - 155100

Опубликована: Сен. 18, 2023

Язык: Английский

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Lutein, a non-provitamin A carotenoid, reduces cisplatin-induced cardiotoxicity

Prostaglandins & Other Lipid Mediators, Год журнала: 2025, Номер unknown, С. 106965 - 106965

Опубликована: Янв. 1, 2025

Язык: Английский

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Biomimetic Sealing of Cisplatin by Cancer Cell Membranes to Achieve Nucleophile Resistance and Tumor Targeting for Improved Cancer Therapy

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Platinum-based anticancer drugs (PBCs), particularly cisplatin, play a key role in over 70% of cancer treatment protocols. PBCs suffer from their strong affinity with numerous nucleophiles present the body, leading to significant systematic toxicity and rapid drug inactivation. The cell membrane's selective energy-dependent transport properties, inherent its unique biological structure, offer strategic opportunity for employing membranes (CMs) development PBC delivery systems that repel nucleophiles. To prove this idea, we harness CMs develop dual-package approach sealing cisplatin nanoformulation is both nucleophile-resistant tumor-targeted without need synthetic materials. process begins by conjugating CMs, creating positively charged nanoparticles. These isolated nanoparticles are then recomplexed CMs. Our strategy, which tightly seals within ensures safely sequestered reactive molecules body while simultaneously guiding it specifically homologous tumors. resulting demonstrates immune evasion prolonged circulation time due native-like identity conferred biomimetic prevented transmembrane attack nucleophiles, including not only macromolecular proteins but also small-molecule compounds such as glutathione, thereby ensuring high level cytotoxicity when challenged these It displays precise targeting at tumors, sustained release, achieves tumor suppression. features together adumbrate nanoformulation's potential revolutionary tool therapy. Given prevalence metal ion-based common susceptibility nucleophile-associated issues, strategy presented study may widely applicable solution developing metal-ion-based medications.

Язык: Английский

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A Comparison of XGBoost, Random Forest, and Nomograph for the Prediction of Disease Severity in Patients With COVID-19 Pneumonia: Implications of Cytokine and Immune Cell Profile

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Апрель 12, 2022

Background and Aims The aim of this study was to apply machine learning models a nomogram differentiate critically ill from non-critically COVID-19 pneumonia patients. Methods Clinical symptoms signs, laboratory parameters, cytokine profile, immune cellular data 63 patients were retrospectively reviewed. Outcomes followed up until Mar 12, 2020. A logistic regression function (LR model), Random Forest, XGBoost developed. performance these measured by area under receiver operating characteristic curve (AUC) analysis. Results Univariate analysis revealed that there difference between with respect levels interleukin-6, interleukin-10, T cells, CD4 + T, CD8 cells. Interleukin-10 an AUC 0.86 most useful predictor pneumonia. Ten variables (respiratory rate, neutrophil counts, aspartate transaminase, albumin, serum procalcitonin, D-dimer B-type natriuretic peptide, interleukin-6 interleukin-10) used as candidate predictors for LR model, Forest (RF) model application. coefficients utilized build nomogram. RF methods suggested the important severity illness prediction. mean LR, RF, 0.91, 0.89, 0.93 respectively (in two-fold cross-validation). Individualized prediction explained local interpretable model-agnostic explanations (LIME) plot. Conclusions exhibited highest discriminatory It is inferred visualized interpretation LIME plot could be in clinical setting. Additionally, interleukin-10 serve

Язык: Английский

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Repurposing FDA-approved drugs against the toxicity of platinum-based anticancer drugs

Life Sciences, Год журнала: 2022, Номер 305, С. 120789 - 120789

Опубликована: Июль 9, 2022

Язык: Английский

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A review on dynamic pharmacological potency and multifaceted biological activities of propolis

Discover Sustainability, Год журнала: 2024, Номер 5(1)

Опубликована: Авг. 8, 2024

Abstract This review explores the therapeutic potential of propolis, a natural resin produced by bees, analyzing recent literature spanning from 2005 to 2023. Various databases including Google Scholar, Web Science, Science Direct, PubMed, SCOPUS, and WoS were searched uncover findings. Propolis exhibits diverse array pharmacological properties, antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, wound-healing effects. It shows promise in treating respiratory infections, oral diseases, gastrointestinal disorders, skin conditions. Additionally, research suggests its as an anticancer agent. The also investigates efficacy propolis addressing antiviral, antibacterial, metabolic disorders (diabetes), reproductive disorder (PCOS), cardiovascular hepatotoxicity, wound healing properties propolis. Hence, could emerge remedy with significant for enhancing healthcare outcomes.

Язык: Английский

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Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy

Nutrients, Год журнала: 2024, Номер 16(21), С. 3741 - 3741

Опубликована: Окт. 31, 2024

Conventional cancer treatments include surgical resection, chemotherapy, hyperthermia, immunotherapy, hormone therapy, and locally targeted therapies such as radiation therapy. Standard often require the use of multiple agents, which can activate nuclear factor kappa B (NF-κB) in tumor cells, leading to reduced cell death increased drug resistance. Moreover, agents also contributes added toxicity, resulting poor treatment outcomes. Cancer cells gradually develop resistance almost all chemotherapeutics through various mechanisms, efflux, alterations metabolism transport, changes signal transduction pathways, enhanced DNA repair capacity, evasion apoptosis, mutations, reactivation targets, interaction with microenvironment, cell-stroma interactions, epithelial–mesenchymal transition (EMT)-mediated chemoresistance, epigenetic modifications, metabolic alterations, effect stem (CSCs). Developing new strategies improve chemotherapy sensitivity while minimizing side effects is essential for achieving better therapeutic outcomes enhancing patients’ quality life. One promising approach involves combining conventional propolis its flavonoids. These natural compounds may enhance response reducing toxicity. Propolis components sensitize chemotherapeutic likely by inhibiting NF-κB activation, reprogramming tumor-associated macrophages (TAMs; an M2-like phenotype), thereby release matrix metalloproteinase (MMP)-9, cytokines, chemokines, vascular endothelial growth (VEGF). By TAMs, overcome EMT-mediated disrupt crosstalk between CSCs, inhibit maintenance stemness, reverse acquired immunosuppression, thus promoting antitumor mediated cytotoxic T-cells. This review highlights potential flavonoids modulate responsiveness modalities. The evidence suggests that novel incorporating could be developed positive cytotoxicity peripheral blood leukocytes, liver, kidney cells. Therefore, polyphenolic/flavonoid hold combination clinical types cancers.

Язык: Английский

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Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin‐Induced Organ Dysfunction in Rats: Comprehensive in vivo and in silico Studies

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(5)

Опубликована: Фев. 16, 2024

Abstract This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)‐induced hepatorenal complications in Wister albino rats. Additionally, it aims detect polyphenolic compounds using high‐performance liquid chromatography with diode‐array detection (HPLC‐DAD). The rats were treated intraperitoneally CP (7.5 mg/kg) mediate damage. They then GP (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although significantly ameliorated CP‐mediated biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate (AST), creatinine, blood urea nitrogen (BUN) levels a dose‐dependent manner, at mg/kg dose normalized ALP (45.11 U/L), ALT (34 AST (29 creatinine (10.3 mg/dl) BUN (11.19 while comparing control disease group. Similarly, though reduced CP‐induced oxidative stress inducers, including nitric oxide (NO) advanced protein products (AOPP), higher (150 exhibited better activity reducing NO (281.54 mmol/gm tissue liver 52.73 kidney) AOPP (770.95 mmol/mg 651.90 kidney). Besides, showed enhancement antioxidant enzymes superoxide dismutase, glutathione mg/kg). Histopathological studies that caused collagen accumulation kidney tissues. drained mass acted Ellagic acid, gallic quercetin hydrate, kaempferol, rutin hydrate revealed extract. In‐silico modelling good docking scores molecular targets CYP4502E1, NF‐κB, caspase‐3, TNF‐α. could be an effective therapeutic option management anticancer drugs’ organ damage, although clinical are required establish herbal formulation.

Язык: Английский

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