Search Results (4,769)

This systematic review aimed to synthesize experimental evidence on the anticancer effects of Lacticaseibacillus rhamnosus (L. rhamnosus) and its derivatives against colorectal cancer (CRC) cell models. Eligible studies investigated probiotics, postbiotics, or bioactive compounds derived from L. rhamnosus with an in vitro component; studies relying solely on in vivo animal models, clinical trials, or observational designs were excluded. PubMed and Scopus were searched to identify relevant studies. Risk of bias was assessed using a modified QUIN tool, and extracted data were tabulated. Owing to incomplete numerical data, meta-analysis was not feasible, and the results were synthesized accordingly. Seventeen studies were included. L. rhamnosus and its derivatives reduced CRC cell proliferation, induced apoptosis, and caused cell cycle arrest. Reported mechanisms included upregulation of Bax, caspase-3/9, and p53; downregulation of Bcl-2/Bcl-xl; inhibition of Wnt/β-catenin signaling; reduced invasion and migration; increased reactive oxygen species; and immunomodulatory effects. Key limitations were heterogeneity in interventions, dosages, exposure periods, and cell lines, along with incomplete reporting, which precluded quantitative synthesis. Overall, preclinical evidence indicates multimodal anticancer effects of L. rhamnosus in CRC models; however, standardized reporting and translational research are required. Full article

Introduction: PMBCL is an aggressive type of lymphoma characterized by high heterogeneity in clinical, molecular, and genetic features. In PMBCL, disturbances in the NFkB pathway and deregulation of BCL-2 and mTOR family proteins are observed, which may contribute to impaired apoptosis. Therefore, many strategies have been established to target the functioning of these pathways. Early clinical trials of mTOR, NFkB and Bcl-2 inhibitors suggest their activity in many hematological cancers, but their activity as monotherapy agents may still be insufficient; therefore, combinations of these compounds with other molecules acting on those active in a given cancer subtype are being sought. Materials and Methods: In vitro studies were conducted on a single PMBCL cell line, Karpas 1106P. We administered three novel drugs: AZD2014 (vistusertib), an inhibitor of the serine-threonine kinase mTOR; IMD-0354, an NFκB inhibitor; and ABT-199 (venetoclax), a highly selective inhibitor for BCL-2. Drugs were administered alone, in pairs and in combination of all three agents. Results: Based on the results of our own research, for the Karpas cell line individually, ABT-199 had the strongest pro-apoptotic effect on cancer cells, while in pairs the most potent induction of apoptosis occurred following treatment with AZD2014+ABT-199. The combination of three drugs did not have a stronger effect than either a single drug used alone or any two-drug combination. Conclusions: These results provide preliminary in vitro evidence that targeting the BCL-2 and mTOR pathways may enhance pro-apoptotic activity in a PMBCL cell model; however, further validation in additional cell lines and in vivo models is needed before translational implications can be considered. Full article

Eriodictyol, a naturally occurring flavanone, has appeared as a biologically versatile compound with increasing relevance in biomedical research, especially in cancers. Evidence over the past few decades indicates that eriodictyol influences cancer cell fate through coordinated modulation of cell-cycle control, survival, and regulated cell death pathways. Eriodictyol appears to reshape oncogenic signaling networks, including PI3K/Akt/mTOR and associated kinase cascades, thereby restricting proliferative capacity and lowering resistance thresholds. Studies consistently report cell-cycle arrest at critical checkpoints, accompanied by activation of both mitochondrial- and death-receptor-mediated apoptotic pathways through disruption of BCL-2 family balance, caspase engagement, and mitochondrial destabilization. Furthermore, eriodictyol alters intracellular redox dynamics in a dose-dependent manner, selectively sensitizing cancer cells to oxidative and metabolic stress. More recent findings extend its significance to inflammation-driven tumor progression and to the regulation of ferroptosis. Beyond intrinsic pharmacological activity, advances in nanocarrier-based delivery and balanced combination strategies have started to address critical challenges and limitations regarding solubility and bioavailability, while allowing precise therapeutic applications. In this review, we have discussed the plausible mechanisms, experimental evidence, and translational insights of eriodictyol as a systems-level modulator of cancer biology. We also outlined research priorities essential for progressing its clinical relevance as future perspectives. Full article

Agapanthus africanus (L.) Hoffmanns. is a medicinal plant traditionally used in South Africa for its promise as a source of bioactive compounds with anticancer properties. This study aimed to investigate the apoptotic effects of A. africanus fractions on cancer cell lines and to identify the bioactive phytochemical constituents using gas chromatography-mass spectrometry analysis. To test for cytotoxicity, MCF-7, A549, and HeLa cancer cells were treated with crude extract, n-hexane, n-butanol, dichloromethane, and aqueous fractions of A. africanus extracts at different concentrations (0.00–1000 µg/mL). Total apoptosis was quantified using Annexin V/PI staining. The 4′,6-diamidino-2-phenylindole was used to detect nuclear morphological changes and the Caspase-GLO 3/7 assay was employed to check the caspase activation in the cancer cells. Expression of apoptosis-related (caspase-3, bax, bcl-2) genes was evaluated using real time-polymerase chain reaction. The crude extract of A. africanus exhibited dose-dependent cytotoxicity against MCF-7, A549, and HeLa cells, with IC₅₀ values of 130 µg/mL, 380 µg/mL, and <125 µg/mL, respectively. Among the tested fractions, the n-butanol fraction showed cytotoxicity towards MCF-7 cells with an IC₅₀ value of <870 µg/mL. In contrast, n-hexane, dichloromethane and the aqueous fractions exhibited higher IC₅₀ values against cancer cells. Flow cytometry analysis, which was applied to quantify total apoptosis, revealed that the crude extract of A. africanus induced apoptosis by (~60%) compared to the n-butanol fraction, which exhibited a moderate apoptotic effect (~27%). DAPI nuclear staining showed nuclear shrinkage and chromatin condensation in the MCF-7 cell line, whereas in Caspase-GLO 3/7, the crude extract and n-butanol fraction resulted in significant luminescence, indicating activation of caspase-3/7. Caspase-3/7 analysis showed A. africanus treatments produced varying levels of apoptotic activation. The crude extract increased caspase activity by 2.9-fold, while the n-butanol fraction induced a 1.7-fold rise compared with untreated cells. GC-MS chromatograms detected and identified 16 compounds in the fractionated n-butanol and 23 compounds from the crude extract of A. africanus. The major compounds identified from the n-butanol fraction included n-hexadecanoic acid; α-tocopherol and 9,12,15-octadecatrienoic acid, while the GC–MS profile of the crude extract was dominated by 6,10,14-trimethylpentadecan-2-one; 1,3,5-Triphenylcyclohexane and phytol. The study indicates the pro-apoptotic potential of A. africanus, particularly in its crude form, supporting its ethnopharmacological use and suggesting its relevance as a candidate for anticancer drug discovery. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) accumulation, oxidative stress (OS), and chronic inflammation drive synaptic dysfunction and cognitive decline. Molecular hydrogen (H₂) has emerged as a candidate neuroprotective gas with selective antioxidant and anti-inflammatory properties, although its efficacy in amyloid-driven pathology remains incompletely defined. In this study, 5xFAD transgenic mice harboring human amyloid precursor protein (APP) and presenilin-1 (PSEN1) mutations and age-matched C57BL/6 wild-type mice were exposed to 2% H₂ by inhalation for 1 h/day over 4 weeks. H₂ inhalation reduced hippocampal reactive oxygen species (ROS), increased systemic catalase activity, and enhanced hippocampal ATP levels. In serum, H₂ decreased tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, restored IL-10, and partially normalized IL-13, shifting the peripheral environment toward a less pro-inflammatory profile. In the hippocampus, H₂ upregulated nuclear factor erythroid 2-related factor 2 (NRF2), attenuated nuclear factor kappa B (NF-κB) activation, reduced the BAX/BCL-2 ratio, preserved neuronal nuclei (NEUN) expression, and decreased hippocampal Aβ42 burden. Collectively, these findings indicate that H₂ inhalation confers multi-faceted neuroprotection in 5xFAD mice by restoring redox homeostasis, suppressing inflammation, improving mitochondrial function, and limiting Aβ accumulation. Full article

For decades, induction treatment of acute myeloid leukemia consisted of intensive chemotherapy for induction. High relapse rates and severe toxicity resulted in a five-year overall survival of ~30%. In patients ineligible for intensive treatment, hypomethylating agents (HMA) could be administered but generally failed to induce durable remissions. These limitations have driven the development of targeted drugs and less toxic therapeutic regimens. In the past decade, fourteen new agents have gained FDA and/or EMA approval, including small-molecule inhibitors targeting FLT3, IDH1, IDH2, BCL-2, menin, and the hedgehog pathway, as well as a CD33-directed antibody-drug conjugate. The combination of targeted drugs with intensive chemotherapy or HMA has resulted in improved remission rates and prolonged survival in certain patient subpopulations. However, many promising combinations are currently being evaluated in randomized trials and are not yet available in clinical routine. A combination that has become standard of care is HMA plus venetoclax for patients unfit for intensive chemotherapy, achieving high remission rates with relatively manageable toxicity. Moreover, targeted drugs directed against FLT3 and IDH1 have been approved in combination with intensive chemotherapy and HMA, respectively. Clinical decision-making requires rapid molecular diagnostic testing, assessment of a patient’s fitness for intensive chemotherapy, and management of toxicities and drug interactions. This narrative review, illustrated with patient vignettes, summarizes currently available therapies, guides through the latest trials on frontline combinations in AML, and provides a preview of how the therapeutic landscape may evolve in the near future. Full article

This study investigated the bioactive properties of fractions derived from Rhynchosia nulubilis cultivated with Ganoderma lucidum mycelium (RNGM), focusing on cytotoxic and apoptosis-related responses in cancer cells. Fractions obtained using n-hexane, chloroform, ethyl acetate, and water were evaluated for cytotoxic effects against A549, Hep3B, HeLa, and HeLa229 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phenolic acid composition of each fraction was determined by high-performance liquid chromatography (HPLC). Among the fractions, the ethyl acetate fraction showed the highest total phenolic acid content and exhibited the strongest cytotoxic activity, particularly against HeLa cells. Apoptosis induction was supported by increased caspase-3/7 activity, apoptotic nuclear morphology observed by 4′,6-diamidino-2-phenylindole (DAPI) staining, and accumulation of cells in the sub-G1 phase. In addition, treatment with the ethyl acetate fraction upregulated p53 and Bax mRNA expression and increased the Bax/Bcl-2 ratio. These findings suggest that the ethyl acetate fraction of RNGM induces apoptosis-mediated growth inhibition in cervical cancer cells. Full article

Gelatin hydrolysate (GH), a bioactive compound derived from collagen, has demonstrated potential therapeutic benefits in various medical conditions. However, its effects on chronic cerebral hypoperfusion-induced vascular dementia remain underexplored. This study aimed to investigate the anti-oxidative stress effects of GH in alleviating brain damage and cognitive impairment in CCH-induced rats. Male Wistar rats underwent bilateral common carotid artery occlusion to induce CCH and were randomly divided into five groups: (1) sham, (2) 2-vessel occlusion (2VO), (3) 2VO + 250 mg/kg GH, (4) 2VO + 500 mg/kg GH, and (5) 2VO + piracetam. Treatments were administered for 35 days of post-operation. GH treatment significantly mitigated oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS), nitric oxide (NO), and the expression of 4-hydroxynonenal (4-HNE) and NADPH oxidase 4 (NOX4). Furthermore, GH exhibited antioxidant activity by upregulating superoxide dismutase (SOD) levels via nuclear factor E2-related factor 2 (Nrf-2) activation. This, in turn, reduced neuronal apoptosis by decreasing Bax and cleaved-caspase 3 levels and increasing Bcl-2 expression. Additionally, GH treatment ameliorated Tau protein hyperphosphorylation and improved synaptic function. Overall, GH exerted neuroprotective effects against oxidative stress-related neuronal damage and enhanced neuroplasticity, learning, and memory in rats with CCH-induced cognitive impairment. Full article

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them. Full article

Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are commonly used to treat gynecological disorders including menstrual irregularities and infertility, and are known to modulate endoplasmic reticulum (ER) stress. However, the therapeutic potential and molecular mechanisms of FA in the context of POI remain largely unexplored. This study aimed to investigate the protective effects of FA against POI and to elucidate the underlying pharmacological mechanisms. Methods: In vivo, a mouse model of POI was established via a single intraperitoneal injection of cyclophosphamide (CTX; 120 mg/kg), and using FA for 28 days of continuous gavage to observe its therapeutic effect. Ovarian function and pathological changes were assessed by hormone levels, follicle development and oxidative stress (OS) level. In vitro, the effects of FA were examined using 4-hydroperoxy cyclophosphamide (4-OHCP)-treated KGN granulosa cells. Transcriptome sequencing, molecular docking, and molecular dynamics simulations were employed to identify potential targets of FA. Results: Our findings demonstrated that FA administration helped preserve regular estrous cycles, promoted follicle development and hormone secretion, and attenuated OS in both ovarian tissue and granulosa cells (GCs). Transcriptomic profiling combined with molecular docking and molecular dynamics simulations suggested that FA potentially targets key ER stress proteins, specifically Grp78 and Perk. Further in vivo and in vitro experiments confirmed that FA alleviates ER stress by inhibiting the overactivation of the Perk/eIF2α/ATF4/CHOP signaling pathway. Notably, the protective effects of FA were comparable to those of the ER stress inhibitor 4-Phenylbutyric acid (4-PBA) and were reversed by the ER stress activator tunicamycin (TM). Additionally, FA downregulates ERO1α expression, further blocking secondary oxidative damage triggered by ER stress. In KGN cells, FA significantly inhibits 4-OHCP-induced apoptosis and upregulates the anti-apoptotic proteins BCL-2 and BCL-xL, exhibiting efficacy similar to 4-PBA. Conclusions: FA improves ovarian function in CTX-induced POI by coordinately regulating OS and ER stress, inhibiting the Perk/eIF2α/ATF4/CHOP pathway, and suppressing GC apoptosis. These findings provide experimental evidence supporting FA as a potential therapeutic candidate for POI. Full article

Background: Hepatic fibrosis and its progressive form, liver cirrhosis, are dangerously recognized complications of liver injury with limited treatment options. This study evaluated the hepatoprotective effects of ivabradine on thioacetamide (TAA)-induced hepatic fibrosis in rats. Methods: Rats were divided into five groups with 10 rats/group and treated as follows: normal, where rats received 0.5% CMC-Na solution orally; ivabradine control, where rats received only ivabradine (20 mg/kg, once daily, orally) for 6 weeks; TAA, where rats received an intraperitoneal (i.p.) injection of TAA (200 mg/kg) thrice weekly for 6 weeks and daily oral 0.5% CMC-Na solution, and two ivabradine + TAA groups, where two doses of ivabradine were tested. Low (10 mg/kg) and high (20 mg/kg) doses of ivabradine were orally given once daily to each group for 6 weeks concurrently with TAA injection. Results: TAA caused marked elevations in liver enzymes, increased MDA, depletion of antioxidant defenses, activation of NF-κB p65 and pro-inflammatory cytokines, dysregulation of apoptotic markers, and upregulation of the PI3K/AKT/mTOR and TGF-β pathways, accompanied by extensive collagen deposition. Ivabradine produced dose-dependent improvements in biochemical markers of liver function, restored oxidant/antioxidant balance, suppressed NF-κB p65/TNF-α, normalized Bax/Bcl-2/caspase-3 expression, and inhibited PI3K/AKT/mTOR as well as TGF-β signaling, leading to significant attenuation of fibrosis. Conclusions: The current findings indicate that ivabradine exerts potent antioxidant, anti-inflammatory, anti-apoptotic, and antifibrotic actions against TAA-induced hepatic fibrosis. Future clinical studies are recommended to determine whether these protective effects translate to patients with chronic liver disease. Full article

Purpose: Osteotoxicity is a well-recognized adverse effect of Methotrexate (MTX) therapy, primarily driven by oxidative stress and impaired bone remodeling. This study aimed to investigate the protective effects of Tempol, a membrane-permeable nitroxide antioxidant, against MTX-induced osteotoxicity, and to assess how these effects are influenced by ML210, a glutathione peroxidase 4 (GPX4) inhibitor. Methods: Murine osteocyte-like MLO-Y4 cells were treated with MTX alone, Tempol alone, or a combination of MTX with Tempol and ML210. Apoptotic markers (caspase-3, Bax, Bcl-2), MAPK signaling proteins (p-JNK, p-ERK), and oxidative stress parameters (TAS, TOS, SOD, GPx) were measured via ELISA to evaluate the redox and apoptotic responses. Results: MTX significantly induced apoptosis, as evidenced by increased caspase-3 activity and Bax expression, along with decreased Bcl-2 levels. MTX also activated the MAPK pathway by upregulating p-JNK and p-ERK. Furthermore, MTX decreased TAS, SOD, and GPx levels, while increasing TOS. Tempol treatment successfully reversed these effects, restoring apoptotic balance, inhibiting MAPK activation, and enhancing antioxidant capacity. However, co-treatment with ML210 markedly attenuated Tempol’s protective effects, resulting in sustained oxidative stress, elevated apoptotic markers, and persistent MAPK pathway activation. This suggests that Tempol’s cytoprotective actions are dependent on functional GPX4 activity. Conclusion: Tempol exhibits strong potential as an adjunctive antioxidant therapy to counteract MTX-induced osteotoxicity. Nevertheless, its efficacy is significantly influenced by the status of the endogenous antioxidant enzyme GPX4. These findings underscore the need for further investigation into Tempol’s mechanism of action in redox-dependent pathways and its suitability in clinical settings, especially where GPX4 function may be compromised. Full article

Gastrointestinal indolent B-cell lymphomas (GI-iBCLs) are a group of low-grade, slowly progressive malignancies, accounting for approximately 1–4% of all gastrointestinal tumors. They represent the most common type of extranodal indolent B-cell lymphoma. Their clinical presentation often overlaps with that of benign inflammatory conditions, posing diagnostic challenges. In recent years, the incidence of GI-iBCL has been increasing in Asia and Europe, while advances in molecular pathology have facilitated more precise classification. This review systematically summarizes recent progress in understanding the epidemiology, clinical features, pathogenesis, pathological characteristics, treatment, and prognosis of GI-iBCLs, with a specific focus on mucosa-associated lymphoid tissue (MALT) lymphoma and duodenal-type follicular lymphoma (DTFL). We also discuss critical issues such as the risk of histological transformation, treatment optimization for refractory cases, the potential of molecular markers, and the evolving landscape of precision medicine. Full article

Honey, as a natural and nutritious sweetener, is one of the most widely consumed foods worldwide. However, the presence of phytotoxins in honey and the influence of honey’s intrinsic sugar matrix on the toxicity of these phytotoxins remain insufficiently explored. An optimized liquid chromatography–quadrupole trap tandem mass spectrometry method was developed to quantify 17 toxic alkaloids in 150 raw honey samples. Camptothecin was identified for the first time in the tested samples and was the most prevalent contaminant (36% detection, max 3.09 μg/kg), which induced cardiac hypertrophy and impaired cardiac function in zebrafish assays. The honey sugar matrix further potentiated these adverse cardiac effects through exacerbating oxidative stress and upregulating pro-inflammatory and pro-apoptotic gene expression, while natural honey partially mitigated such damage by upregulating the key antioxidant gene nrf2, thereby downregulating il-1β and regulating the bcl2/bax expression ratio. This study offers novel insights into honey phytotoxins’ matrix-modulated toxicity, laying a scientific foundation for optimizing safety protocols and matrix-specific risk standards. Full article

Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3β, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-κB, TNF-α, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary. Full article