TRAIL acts as a selective anticancer agent in non-small cell lung cancer (NSCLC). However, some NSCLC are resistance to TRAIL due to the presence of several anti-apoptotic mechanisms. With the help of natural compound such as curcumin, TRAIL-resistance can be overcome and the effect of TRAIL-induce apoptosis in NSCLC can be improved. In this study, we investigated the effect of curcumin in NSCLC as sensitiser to TRAIL as well as their molecular underlying mechanism. Proliferation assay was conducted to determine whether curcumin could enhance the cytotoxic effect of TRAIL in NSCLC cell lines. Flow cytometry was performed for the assessment of TRAIL receptors expression (DR4 and DR5) and apoptosis assay (Annexin-V / PI staining). Gene expression analysis using RT2 profiler PCR array and KEGG tools were performed to analyse the transcriptional levels of 84 significant apoptotic genes in NSCLC. Treatment of NSCLC cell lines with TRAIL revealed that NSCLC cell lines can be classified as TRAIL-sensitive (H2170 and H1437) and TRAIL-resistant (A549 and H1299) based on their IC50 values. H1299 has slightly lower expression of DR5, as compared to the other NSCLC cell lines which have more than 90% expression of DR4 and DR5. The combined treatment of curcumin and TRAIL were able to reduce cell viability and enhanced apoptosis in both TRAIL resistant and sensitive NSCLC cells than TRAIL alone. In addition, the combined treatment seems to induce the intrinsic apoptotic pathway in P53-deficient H1299, by activating the pro-apoptotic genes which are independent of P53. Hence, this study provides evidence on the potential of curcumin as a sensitiser to enhance the efficacy of TRAIL in NSCLC and in TRAIL-resistance NSCLC.

Plantago major subsp. intermedia has been traditionally used in Türkiye for the treatment of wounds, abscesses, constipation, pain, ulcers, hemorrhoids and gynecological diseases. In the present study, the phytochemical composition of P. major subsp. intermedia (Gilib.) Lange was investigated and its anti-inflammatory and wound healing effects were examined in light of existing experimental evidence from related Plantago species. MeOH, 80% EtOH and water extracts of the plant were prepared. In vivo anti-inflammatory effects of these extracts were investigated using an acetic acid-induced capillary permeability model and their wound healing effects were studied using linear incision and circular excision wound models. Isolation studies were performed on the 80% EtOH extract. Furthermore, in vitro studies were conducted on the 80% EtOH extract, the main fractions obtained from this extract and the some of the isolated pure compounds. In these in vitro studies, anti-inflammatory effects were investigated by measuring nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels and wound healing effects were investigated using the scratch test. A total of six compounds were isolated from P. major subsp. intermedia: Isotachioside (1), aucubin (2), 10-hydroxymajoroside (3), 10-acetoxymajoroside (4), martynoside (5) and acteoside (6). All tested compounds significantly inhibited NO production at concentrations of 25, 50 and 100 µM (12.68%-61.89%). Although in vivo results were not statistically significant, the 80% EtOH extract showed the highest efficacy in linear incision and circular excision wound models. The results of this study indicate the in vitro anti-inflammatory and wound healing activities of P. major subsp. intermedia and are consistent with previously reported biological activities of P. major.

Nurses face demanding work linked to poor mental and physical health. Evidence for Swedish classic massage in this context is limited to short-term trials with passive comparators. Before a randomised controlled trial, feasibility should be evaluated. Guided by Bowen’s feasibility framework, we examined a 12-month, monthly Swedish classic massage programme for nurses, focusing on limited efficacy (stress, mental health, sleep, physical activity, HR-QoL, pain, work ability) and acceptability (recruitment, adherence, satisfaction). An embedded mixed-methods, one-group pre–post design was used. Quantitative outcomes were assessed at baseline, 6 months, and 12 months. Limited efficacy was defined as ≥ 3 target domains with effect sizes ≥ 0.20 at 6 or 12 months. Acceptability was appraised using predefined traffic light criteria (Green, Amber, Red) for recruitment, adherence, and satisfaction. Qualitative data from open-ended questions at 12 months explored participants’ experiences. Twenty-five nurses participated (84% completed follow-up). Recruitment reached 50% of the target (Amber), while adherence and satisfaction met Green thresholds. According to predefined criteria, limited efficacy was achieved, with ≥ 3 target domains exceeding the 0.20 threshold at both 6 and 12 months. Domains contributing to this signal included stress, HR-QoL, work ability, and mental health, with many changes evident by 6 months. Depressive symptoms and exhaustion continued to improve to 12 months, while sleep and sustained pain relief contributed only partially to the limited efficacy signal. Integration of quantitative and qualitative data indicated that perceived reductions in stress, increased emotional balance, and greater capacity to manage work demands aligned with measured outcomes. This feasibility study met predefined acceptability and limited efficacy criteria, except for recruitment. Progression to a larger trial in this format is not warranted; however, modifications such as extended recruitment, repeated invitations, and preference-based designs may improve feasibility. Domains with weaker or inconsistent change may require targeted co-interventions in a future evaluation. ClinicalTrials.gov NCT05555082 • Offering monthly classic massage for nurses was feasible to deliver and was well received, with high adherence and satisfaction. Recruitment was lower than planned, indicating the need for changes to attract more participants. • The study met its predefined criteria, with several outcomes such as stress, quality of life, work ability, and mental health showing consistent positive signals at both 6 and 12 months. Some areas, like sleep and lasting pain relief, showed weaker or less consistent signals. • A larger trial in this exact form is not advised. Future studies should test adjusted recruitment approaches (e.g., longer recruitment periods, reminders, and offering choice between interventions) and add targeted components to address outcomes that were less responsive.

Cervical cancer remains the fourth most common malignancy among women worldwide, with limited therapeutic success in advanced and recurrent stages. Conventional treatments, including radiotherapy and chemotherapeutic agents are often limited by off-target toxicity and poor selectivity toward malignant cells. Considering growing interest in phytotherapeutics, the present study evaluates the cytotoxic and genotoxic effects of methanolic extract of Curcuma caesia (MECC) on cervical cancer cells. Human cervical cancer cell lines (HeLa and SiHa) and non-cancerous HEK293T cells were treated with varying concentrations of MECC. Cell viability, proliferation, and oxidative stress were assessed via MTT, cell cycle analysis, and ROS quantification, respectively. DNA damage and repair responses were evaluated using COMET, TUNEL, and γH2A.X foci assays. Senescence was detected by β-galactosidase staining, while apoptotic and DNA damage response proteins were examined through Western blotting. MECC exhibited dose-dependent cytotoxicity in HeLa and SiHa cells while sparing HEK293T cells, indicating selectivity toward malignant cells. Treatment induced cell cycle arrest and significantly reduced intracellular ROS levels. DNA damage was evident from increased comet tail moments, TUNEL positivity, and nuclear accumulation of γH2A.X. MECC further promoted apoptosis, as demonstrated by elevated levels of cleaved caspase-3, Bax, cleaved PARP1, and reduced Bcl-2 expression. Concurrent induction of cellular senescence was also observed. MECC induces apoptosis and senescence, through modulation of oxidative stress and induction of DNA damage in cervical cancer cells. This highlights its potential as a plant-based therapeutic candidate with reduced cytotoxicity toward non-cancerous cells.

Cisplatin (CIS) is a chemotherapeutic agent which is frequently utilised in the treatment of ovarian, breast, testicular and lung cancer. Nevertheless, the potential for severe and irreversible toxicity to the lungs restricts its utilisation. Naringin (NRG), a flavanone glycoside found in significant quantities in citrus fruits, has been demonstrated to exert protective effects against oxidative tissue damage. The present study aimed to assess the protective effect of NRG against CIS-induced pulmonary toxicity. The administration of NRG (50 and 100 mg/kg) was conducted orally over a period of seven days. CIS (7.5 mg/kg, IP) was administered on day 2 to rats, and lung samples were collected on day 8. The CIS application induced lipid peroxidation (LPO), inflammation, and endoplasmic reticulum stress (ERS) in the lung, resulting in the emergence of histopathological findings. However, the administration of NRG was found to be capable of preventing lung injury by suppressing LPO, inflammation and ERS levels in a dose-dependent manner. Furthermore, the suppression of CIS-induced sirtuin1(SIRT1)/nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling was abolished by NRG supplementation. The present study has shown, for the first time, that NRG has a potential for protection against lung injury by modulating SIRT1/Nrf2/HO-1 signalling in the context of CIS-induced lung injury.

Balneotherapy (BT), involving the use of natural resources such as mineral water, peloids, and climate exposure, is increasingly recognized as a complementary intervention for stress-related mental health conditions. This study aimed to evaluate the short- and long-term effects of a standardized BT complex on stress, anxiety, depression, and related outcomes. A multicenter, randomized, controlled, single-blinded (researchers) parallel-group trial was conducted in six Lithuanian medical spa centers. Adults aged 18–65 years with moderate to high stress levels (N = 243) were randomized into three intervention groups—ambulatory BT (11ABT), ambulatory BT plus nature therapy (11ABTNT), inpatient BT (11BTS)—and one control group (11 C). The treatment period was 11 days, with assessments at baseline, post-intervention, 3 months, and 6 months. Primary outcomes included perceived stress (PSS-10), salivary cortisol, anxiety (STAI-5), and depression (CESD-R). Secondary outcomes were fatigue (FAS), sleep quality (SQS), functional adaptation (WSAS), integrative well-being, cognitive performance, and treatment safety. All intervention groups showed statistically significant improvements across primary and secondary outcomes compared to baseline (p < 0.001), with medium to very large effect sizes. The greatest short-term effects were observed in the inpatient group (11BTS), including reductions of 46% in stress intensity, 54% in depression, and 49% in sleep impairment. Improvements in fatigue, anxiety, and stress management were also notable. These effects persisted at 6 months, with sustained reductions of up to 31% in stress, 27% in anxiety, and 50% in stress management. Sleep quality improved by up to 67%, and integrative outcomes by 40%. No serious adverse events were reported, and treatment was well-tolerated across all sites. Balneotherapy using natural resources is a safe, effective, and sustainable complementary approach for improving mental health. The observed reductions in stress, anxiety, depression, and fatigue—alongside enhanced sleep and functioning—suggest that BT may be a valuable addition to integrative care strategies for stress-related conditions. Further large-scale trials are warranted to confirm these findings and support wider clinical implementation. ClinicalTrials.gov Identifier NCT06018649 (August 25th, 2023).

Maerua edulis (Gilg & Gilg-Ben.) DeWolf) was traditionally used in the treatment and/ or management of various diseases, including cancer. However, limited studies have evaluated whether M. edulis can suppress the proliferation of cervical cancer cells, and its putative mechanism for antiproliferative activity remains unclear. Therefore, we conducted this study to evaluate the in-vitro antiproliferative and cytotoxic effects of M. edulis root extracts against human cervical cancer cells and their underlying mechanism of action. To achieve this goal, we performed MTT assay, microscopic analyses, and wound-healing assay to assess the antiproliferative activity of M. edulis extract and its fractions. Qualitative phytochemical and gas chromatography-mass spectrometry (GC-MS) analyses were performed to characterize the phytochemicals in bioactive extracts, and network pharmacology was utilized to predict putative molecular targets and the mechanism of action of the active extract's fractions. Target validation was accomplished through molecular docking and real-time PCR methods. Bioactive M. edulis extracts exhibited significant antiproliferative activity against HeLa cells, with hexane fraction (essential oil) and ethyl acetate extracts demonstrating IC50 values of 0.02% (v/v) and 47.42µg/mL, respectively. GC-MS analysis identified key phytochemicals such as methyl stearate, (8Z)-14-methylhexadec-8-enal, squalene, and stigmasta-3,5-diene, which were associated with the demonstrated bioactivities, possibly mechanistically through regulation of apoptosis and cell cycle-related genes (BCL2, CDK2, TP53). Interestingly, gene expression analysis revealed the modulation of these target genes. The results of our study suggest the potential therapeutic benefits of M. edulis in the treatment and management of cervical cancer. Further in-vivo studies are recommended to validate these findings and establish their safety profile.

The study was conducted to investigate the immunomodulatory effects of herbal cough medications available on the market that contain either whole plant extracts from ivy, thyme, Pelargonium or the active plant-derived compound cineole on human lung epithelial cells in order to evaluate their potential in the treatment of viral inflammatory processes. Different concentrations of the commercial plant medications (five medications that contained total ivy, thyme or Pelargonium extracts and one plant medication that contains cineole) were analyzed for their cytotoxicity and immunomodulatory potential on the human epithelial lung cancer cell line A549 and the hTERT-immortalized cell line NuLi-1. Viability was tested using WST-1 assays. AnnexinV/PI staining and flow cytometry analysis were used to investigate apoptosis and necrosis. A549 and NuLi-1 cells were stimulated with toll-like receptor (TLR)7- and TLR8-agonists, mimicking viral infection. Cytokine secretion was analyzed using the bead-based LEGENDplex™ assay. Non-toxic concentrations of the ivy-, thyme- or Pelargonium- containing medications, but not the medication containing cineole, significantly reduced the secretion of inflammatory cytokines and chemokines after the stimulation of TLR7 and TLR8 in A549 and NuLi-1 cells. Medications derived from ivy, thyme and Pelargonium extracts exhibit anti-inflammatory properties in a model mimicking viral infection in human lung epithelial cells.