A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC50) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.

Phosphoinositide 3-kinase (PI3K) inhibitors have demonstrated efficacy in cancer therapy; yet, their clinical use is often restricted by off-target toxicity. Peptide-drug conjugates (PDCs) have emerged as a strategy to improve tumor selectivity by targeting receptors overexpressed in malignant cells. Luteinizing hormone-releasing hormone receptors (LHRHR), upregulated in several cancers, present an attractive target for such approaches. In this study, we obtained an LHRHR-targeting peptide IV-6, characterized by high receptor affinity and robust metabolic stability. IV-6 was then conjugated to the PI3K inhibitor buparlisib, forming the target PDC, DiWB-1. In Vitro, DiWB-1 exhibited superior antineoplastic effects against LHRHR-positive MDA-MB-231 cells, with an IC50 of 1.8 μM, compared with 2.4 μM for buparlisib, and demonstrated reduced toxicity in normal cells. In Vivo, DiWB-1 showed considerable tumor-suppressive effects while minimizing systemic toxicity, avoiding the hepatic and renal damage, as well as hyperglycemia, observed with buparlisib treatment. Pharmacokinetic studies further indicated that DiWB-1 had favorable metabolic stability, with a half-life of 5.6 h, slightly exceeding that of triptorelin (4.2 h). These findings suggest that DiWB-1 holds promise as a selective, potent, and long-acting anticancer PDC, warranting further investigation.

Cancer cells exhibit elevated levels of reactive oxygen species, resulting in oxidative stress and DNA damage. To counteract this, many cancers upregulate the expression of MTH1 (MutT Homolog-1), a crucial enzyme that detoxifies oxidised nucleotide pools. Consequently, inhibiting MTH1 is a potential therapeutic strategy for managing DNA damage and cancer cell death. Here, we conducted a comprehensive computational screening of 3800 FDA-approved drugs to identify potential MTH1 inhibitors. Among these, Lumacaftor and Nilotinib were selected based on their strong binding affinity and pharmacokinetic profiles. Molecular dynamics simulations over 500 ns further validated the stable binding of these drugs to MTH1, suggesting their potential as effective inhibitors. Nilotinib, a well-known tyrosine kinase inhibitor (TKI), displayed strong binding affinity (Ka = 2.5 × 104) and potent MTH1 inhibitory activity (IC50: 37.2 μM). Notably, this study is the first to establish the interaction between Nilotinib and MTH1, highlighting the dual potential of Nilotinib as an MTH1 inhibitor. The findings suggest that Nilotinib could be repurposed to enhance cancer therapy, particularly in combating drug resistance through the novel mechanism of MTH1 inhibition. This approach provides new avenues for tackling chemoresistance and improving therapeutic outcomes in cancer patients.

Chemotherapy resistance poses a significant challenge in the initial treatment of acute myeloid leukemia (AML). Growth differentiation factor 15 (GDF-15) has been shown to play a critical role in cancer progression; however, the potential mechanisms by which GDF-15 contributes to AML progression and chemotherapy resistance remain unclear. We found that M2 macrophages secrete high levels of GDF-15, promoting resistance of AML cells to mitoxantrone (MTX). Furthermore, we demonstrated that MTX induces downregulation of the SLC7A11/GPX4 signaling axis in AML cells, mediating ferroptosis. GDF-15 enhances the expression of the SLC7A11/GPX4 axis, thereby inhibiting ferroptosis in AML cells and contributing to drug resistance. In addition, GDF-15 mitigates the decline in mitochondrial membrane potential and mitochondrial quality induced by MTX. In vivo experiments indicate that blocking GDF-15 effectively enhances the sensitivity of AML cells to mitoxantrone by reducing the expression of the SLC7A11/GPX4 axis.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent and debilitating condition observed in cancer patients, especially in those suffering from hematologic malignancies. The present study assessed the efficacy of a compounded mouthwash, both with and without the addition of acyclovir, in the management of CIOM. Although various treatment options exist for this condition, their effectiveness remains limited, underscoring the necessity for innovative approaches to the formulation of compounded mouthwashes for improved management of CIOM.

Medication-Related Osteonecrosis of the Jaw (MRONJ), an established side effect of antiresorptive and antiangiogenic medication, could sometimes require surgical intervention, such as decortication. The objectives of this retrospective patient survey study were to evaluate the effect of surgical treated MRONJ on health-related quality of life (QoL) and to assess the awareness of the risk of MRONJ.

The present research has aimed to formulate fibroin nanoparticles (FNPs) and Bergenia ciliata-loaded fibroin nanoparticles (BCFNPs) to investigate their antitumor activity against breast cancer in mice. The prepared FNPs and BCFNPs characterized by Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Zeta potential measurement, Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). UV-Vis spectroscopy revealed characteristic peak at 282 nm for FNPs and 285 nm for BCFNPs, indicating the successful development of fibroin nanoparticles (FNPs) and Bergenia ciliata-loaded fibroin nanoparticles (BCFNPs). FT-IR analysis identified characteristic absorption bands in the FNPs spectrum at 3350 cm-1, 1654 cm-1, 1587 cm-1, and 1087 cm-1, indicating the preserved secondary structure of fibroin. In the BCFNPs spectrum, peak shifts and intensity variations were observed at 3338 cm-1 and 1180 cm-1 due to the loading of the bioactive compound, indicating successful incorporation of B. ciliata. The DLS analysis confirmed that the FNPs were within the nanometer size range, while the zeta potential measurements indicated that FNPs and BCFNPs have slightly negative surface charge. The SEM analysis assessed the shapes of nanoparticles ranging from round, triangular, and hexagonal shapes and XRD peaks at 2ϴ (20-80) confirmed crystalline nature of FNPs and BCFNPs. In the present study, we established a mice model (Swiss albino) of breast cancer induced by CdCl2 and treated with tamoxifen, Bergenia ciliata, FNP, and BCFNP to access their antitumor activity. During breast cancer induction, CdCl2 treated groups experienced weight loss, dropping from 30.2 to 18.0 g. After two months, administration of BCFNP significantly inversed the alteration of body weight. At the end of the trial, levels of blood serum biomarkers analyzed. All treatment groups showed better results but BCFNPs treated group exhibited significant reduction (P < 0.0001) in TNF-α (31.7 ± 1.4 pg/ml), IL-6 (20.2 ± 0.9 pg/mL), IL-10 (25.4 ± 1.9 pg/mL), LDH (481.0 ± 7.5 μmol/ml), ASAT (179.0 ± 7.3 μmol/ml), ALAT (532.8 ± 13.4 μmol/ml), and ALP (164.8 ± 5.9 μmol/ml) along with reduced tumor volume. Moreover, Significant (P < 0.0001) improvements in GSH and MDA (248.6 ± 7.9 μmol/ml) serum biomarkers also found. Histological analysis of the BCFNPs treated group revealed a significant reduction in ductal carcinoma. In conclusion, Bergenia ciliata loaded fibroin nanoparticles have potent potential to treat tumors by targeted drug delivery.

Survival after a cancer diagnosis is improving, increasing the importance of understanding and managing long-term treatment-related adverse effects. This study aimed to understand breast and prostate cancer survivors' understanding of how cancer treatment may affect cardiovascular and musculoskeletal health.

Clinician-assessed performance status is a strong predictor of morbidity in cancer patients, but it lacks patients' perspective. This study aims to examine the agreement between clinician (cPS) and patient (pPS) in reporting performance status and identify which assessment better predicts 30-day morbidity.

Cisplatin, a widely used therapy for solid tumors, is associated with hepatotoxicity characterized by cytoplasmic vacuolization of liver cells, sinusoidal congestion, mononuclear and Kupffer cell infiltration, and focal necrosis. Moringa oleifera (M. oleifera) leaves, rich in flavonoids with antioxidant properties, may mitigate hepatotoxicity. This study aimed to evaluate the effects of ethanol extract of M. oleifera leaves on inflammation, oxidative stress, and liver cell damage in a rat model of cisplatin-induced hepatotoxicity.

Oral squamous cell carcinoma (OSCC), affecting the lip and oral cavity, is one of the most prevalent cancers worldwide with the highest morbidity rate in the North-Eastern region of India. The current treatment options including surgery and chemotherapy are plagued by adverse side-effects and emergence of chemo-resistance, particularly against drugs like cisplatin and 5-fluorouracil. The present study focuses on demonstrating the effects of diosgenin, a naturally occurring steroidal saponin, on the survival, proliferation, and migration of OSCC cells in vitro.

There are international studies that examine the effects of laughter yoga on the symptoms and quality of life of cancer patients as a complementary therapeutic method.

Paclitaxel (PTX) is a potent chemotherapeutic agent limited by poor solubility and adverse effects. To address these challenges, we developed a novel nanocomposite combining PTX purified from the endophytic fungus A. fumigatiaffinis PP235788.1 with biosynthesized silver nanoparticles (AgNPs) from the same fungal strain. The PTX-AgNP conjugate (28.48 ± 0.13 nm) was characterized by UV-Vis, XRD, and TEM, revealing monodisperse AgNPs (14.50 ± 0.58 nm) as the core component. In vitro studies demonstrated significant cytotoxicity against MCF-7 breast cancer cells (IC₅₀= 1.7 µg/mL, p < 0.001), with 5-10-fold greater efficacy than AgNPs alone. Annexin V/PI staining and DNA fragmentation assays confirmed apoptosis induction, highlighting the conjugate's enhanced anticancer activity. This eco-friendly nano platform synergizes PTX's therapeutic effects with AgNP-mediated targeting, offering a promising strategy to reduce side effects while improving tumor-specific cytotoxicity for advanced cancer therapy.

This study aims to evaluate the frequency of hemorrhagic complications and identify potential risk factors in premature infants treated with intravitreal bevacizumab for retinopathy of prematurity (ROP).

Sesquiterpenoids are widely distributed in plants, animals, marine organisms and microorganisms, particularly in Asteraceae plants, and they exhibit various biological activities, including anti‑tumor, anti‑bacterial, anti‑inflammatory, antiviral and antioxidant properties. They also have the effects of protecting the liver, protecting the nerves, preventing and treating diabetes and improving immunosuppressive function. Hepatocellular carcinoma (HCC) is the main type of primary liver cancer and the third leading cause of cancer‑related death worldwide. There is accumulating evidence that HCC is an increasingly serious threat to human health and the incidence of primary liver cancer is also still increasing. For the present review, literature on sesquiterpenoids in the treatment of liver cancer from 2003 to 2024 was searched through electronic databases. A total of 46 sesquiterpenoids were identified for HCC treatment. It was found that sesquiterpenoids play a therapeutic role in HCC by inhibiting proliferation, inducing apoptosis, inhibiting invasion and metastasis of HCC cells, regulating the body's immune function and decreasing the resistance of tumor cells. Sesquiterpenoids are promising drugs, which may create more opportunities for the treatment of liver cancer. However, research on how sesquiterpenoids act on HCC is not systematic and most reports are also limited to mixtures, while there is only a small number of reports of new sesquiterpene monomers for treating HCC. Therefore, it is necessary to further discover new components and study their biological activities, and to gradually conduct in‑depth in vivo studies and clinical application in the future. The present study reviewed the research progress of sesquiterpene‑rich natural products in the treatment of HCC in the past two decades.

STAT3 is abnormally activated in several types of cancer, and elevated nuclear levels of STAT3 are strongly associated with poor prognosis in oral squamous cell carcinoma (OSCC). Despite ongoing progress in developing targeted therapies, there is no Food and Drug Administration‑approved drug currently targeting STAT3 in OSCC. To evaluate the anticancer effects of BBI608, a potent STAT3 inhibitor, in two human OSCC cell lines (HSC‑3 and HSC‑4), various two‑dimensional (2D) or 3D in vitro analyses were performed, including western blot analysis, colony formation assay, DAPI staining, sub‑G1 population analysis and Annexin V/PI staining. The molecular mechanisms of BBI608 were also determined using cross‑linking assay, nuclear and cytoplasmic fractionation assay, reverse transcription‑quantitative PCR and chromatin immunoprecipitation assay. In the present study, it was observed that human HSC‑3 and HSC‑4 OSCC cells exhibited higher levels of phosphorylated (p)‑STAT3 compared with those in immortalized oral keratinocytes (iHOK cells). BBI608 inhibited cell proliferation in a concentration‑dependent manner and triggered caspase 3‑dependent apoptosis in HSC‑3 and HSC‑4 cells. Additionally, BBI608 reduced the nuclear translocation of p‑STAT3 in HSC‑3 and HSC‑4 cells compared with that in DMSO‑treated cells. Mechanistically, BBI608 modulated anti‑apoptotic STAT3 downstream genes: Survivin expression was regulated at the transcriptional level, while myeloid cell leukemia‑1 expression was modulated post‑translation via proteasomal degradation. Consistent with the results from 2D culture, BBI608 showed effective anticancer effects against OSCC spheroids in 3D culture. These results suggest that BBI608 effectively inhibits STAT3 activation in both 2D and 3D models, offering a promising therapeutic strategy and supporting its potential for repurposing in patients with OSCC who exhibit elevated STAT3 activity.

ObjectiveTo evaluate changes in intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) following intravitreal anti-VEGF injections (IVI) and to assess influencing factors.MethodsIn a prospective study, 119 eyes received anti-VEGF IVI, with 60 eyes treated in the supine position and 59 eyes in the seated position. IOP was assessed using an iCare IC200 rebound tonometer before, immediately after, and at 5 and 30 min post-injection. MOPP was calculated at the same time points. Ocular biometric and demographic data were collected to analyze their impact on IOP changes.ResultsIOP increased from 15.76 ± 4.34 mmHg at baseline to 49.79 ± 15.73 immidiately post-IVI, then decreased to 29.96 ± 10.55 at 5 min and 21.80 ± 7.36 at 30 min. MOPP dropped from 54.02 ± 10.7 mmHg to 35.7 ± 19.7 mmHg immediately post-IVI, recovering to 40.68 ± 15.9 at 5 min and 51.08 ± 12.2 at 30 min. Supine patients exhibited higher IOP, but maintained higher MOPP compared to seated patients. Only 25% of glaucoma patients returned to baseline IOP within 30 min, compared to 48.9% of non-glaucomatous patients (p = 0.02). Phakic patients have greater IOP changes across time, with significant differences at 5 min (p = 0.03).ConclusionIVI induced IOP increases and MOPP decreases are significant but normalized to baseline +2SD within 30 min in 67.77% and 97.52% of patients. Glaucomatous and phakic patients are at higher risk for prolonged IOP elevation, requiring careful management.

Immune checkpoint inhibitors (ICI) have revolutionized the therapeutic direction for lung cancer, yet their response rates remain unsatisfactory. Recently, the combination of ICI and low dose radiotherapy (LDR), a novel approach that effectively mobilizes innate and adaptive immunity, has gained interest among scientists. However, the underlying molecular mechanisms are not clearly elucidated.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy with limited treatment options, particularly for patients with advanced stages of the disease. Sorafenib, the standard first-line therapy, faces significant challenges due to the development of drug resistance. Yu et al explored the mechanisms by which lncRNA KIF9-AS1 regulates the stemness and sorafenib resistance in HCC using a combination of cell culture, transfection, RNA immunoprecipitation, co-immunoprecipitation, and xenograft tumor models. They demonstrate that N6-methyladenosine-modified long non-coding RNA KIF9-AS1 acts as an oncogene in HCC. This modification involves methyltransferase-like 3 and insulin-like growth factor 2 mRNA-binding protein 1, which play critical roles in regulating KIF9-AS1. Furthermore, KIF9-AS1 stabilizes and upregulates short stature homeobox 2 by promoting its deubiquitination through ubiquitin-specific peptidase 1, thereby enhancing stemness and contributing to sorafenib resistance in HCC cells. These findings provide a theoretical basis for KIF9-AS1 as a diagnostic marker and therapeutic target for HCC, highlighting the need for further investigation into its clinical application potential.

Oxaliplatin resistance remains a significant clinical challenge in colorectal cancer (CRC), highlighting the urgent need to identify novel molecular targets for therapeutic intervention. Recent findings by Niu et al have elucidated the role of the NAD+/SIRT1 axis in mediating oxaliplatin resistance through metabolic reprogramming. Their study demonstrated that oxaliplatin-induced DNA damage activates PARP, resulting in NAD+ depletion and subsequent downregulation of SIRT1. This reduction in SIRT1 levels enhances glycolysis, as evidenced by increased expression of PKM2 and LDHA, thereby conferring a metabolic advantage to resistant CRC cells. Conversely, restoration of SIRT1 expression reverses resistance, while pharmacological inhibition of glycolysis effectively sensitizes cells to oxaliplatin. These findings underscore the therapeutic potential of targeting the NAD+/SIRT1 pathway as a metabolic vulnerability in CRC. Future studies should investigate the clinical feasibility of combining SIRT1 agonists and glycolysis inhibitors with oxaliplatin to overcome drug resistance and improve patient outcomes.