BackgroundLorundrostat, an aldosterone synthase inhibitor, shows promise for hypertension management, though optimal dosing strategies remain poorly defined.AimsTo evaluate the efficacy, safety, and dose-response effects of Lorundrostat to identify the optimal therapeutic dose.MethodsWe searched PubMed, Embase, Scopus, and ClinicalTrials.gov systematically for relevant RCTs. Using a random-effects model, data were pooled to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs). Dose-response modeling was performed using “dosresmeta” and “rcs” packages in R (v4.4.3).ResultsThree RCTs (n=1568) were included. Lorundrostat significantly reduced systolic BP at 4–8 weeks (MD: –7.66 mmHg, 95% CI: –10.42 to –4.89) and 12 weeks (MD: –10.19 mmHg, 95% CI: –13.57 to –6.82). Diastolic BP also decreased significantly (MD: –3.81). Sub-group analysis based on background medication count showed no significant differences (P=0.80). Aldosterone levels were significantly reduced (MD: –4.39). Dose-response modeling identified 60 mg as the optimal dose, with diminishing returns thereafter. While hyperkalemia risk increased (RR: 3.19), no significant differences were found in serious adverse events.ConclusionLorundrostat effectively lowers BP with a manageable safety profile. The modeling-based insights suggest 60 mg as the optimal dose, delineating a clearer therapeutic window.

Recent articles and news blogs have been written about nuclear waste management, specifically focusing on the alleged hazards of iodine-129. Here, we objectively review the specific details of iodine-129 as a radiation hazard. In contrast with the alarmist tone of these recent papers and news items, we conclude that iodine-129 is not nearly as concerning as has been projected. Rather, it appears to be a classic case of “much ado about nothing”.

Gastrointestinal malignancies, which arise from multiple etiological factors, are a global health burden due to their high incidence and mortality rates. Nearly all gastrointestinal cancers present genomic and epigenomic alterations that play a critical role in initiating and driving tumor progression. N6-methyladenosine (m6A) methylation, a key epigenetic modification in eukaryotic messenger RNA (mRNA), is pivotal for regulating various cellular biological processes and influences both the progression and prognosis of diverse diseases. In gastrointestinal cancers, m6A methylation is closely associated with tumor proliferation, invasion, metastasis, and radiosensitivity. This review aims to uncover the translational regulatory mechanisms mediated by m6A methylation in gastrointestinal cancers and to clarify its role in radiotherapy, as well as to identify potential molecular targets for improving the efficacy of radiotherapy in treating gastrointestinal tumors.

PurposeFLASH radiotherapy (FLASH-RT) has been reported to spare skin from acute radiation toxicity. However, systematic quantification is needed to determine the dose and dose-rate thresholds necessary for optimal radioprotection in FLASH radiotherapy.Materials and MethodsThe hind limbs of male C57BL/6J mice were irradiated with a single-fraction dose (18-24 Gy) delivered using either FLASH-RT (ultrahigh dose rate: 250 Gy/s) or conventional radiotherapy (CONV-RT: 0.1 Gy/s) in the dose optimization experiment. Subsequent studies included a dose-rate optimization trial comparing FLASH-RT (40-400 Gy/s) with CONV-RT at 20 Gy; the antitumor efficacy of a single 20 Gy dose delivered via FLASH-RT (300 Gy/s) was compared with that of CONV-RT; and an assessment of the reirradiation response using FLASH-RT (400 Gy/s) or CONV-RT at 20 Gy following a prior hypofractionated CONV-RT regimen (9 Gy × 4). Skin injury scores, tumor volume, and body weight were monitored longitudinally for up to 30 days after irradiation or until the experimental endpoint was reached. Tumor weight and lung metastasis nodules were measured at the endpoint.ResultsDry desquamation, alopecia, moist desquamation, hemorrhage, full-thickness necrosis, and ulceration were observed more frequently in the CONV-RT group than in the FLASH-RT group. Compared with CONV-RT, FLASH-RT resulted in significantly lower acute skin injury scores at doses ≤22 Gy (18 Gy, 20 Gy, 22 Gy, P < 0.001), but this protective effect was absent at doses ≥24 Gy. Dose-rate optimization (40-400 Gy/s) delivering a 20 Gy dose revealed that acute skin injury scores were significantly reduced only at the higher dose-rates (≥300 Gy/s, compared with CONV-RT, P < 0.001), whereas no significant reduction was observed at the lower dose-rates (≤200 Gy/s, P ≥ 0.05). No additional benefit was detected between 300 Gy/s and 400 Gy/s. Although 250 Gy/s provided significant radioprotection compared with CONV-RT (P < 0.01), it was not the minimal rate required for maximal protection, as evidenced by a significantly better outcome at 300 Gy/s at 24 days (P = 0.0296). Finally, in B16/F10 cell-transplanted mouse models, FLASH-RT (300 and 400 Gy/s) achieved tumor control equivalent to that of CONV-RT while also reducing lung metastasis nodules and significantly mitigating acute skin toxicity (P < 0.001) during reirradiation.ConclusionsIn this study, a dual-threshold framework was established to guide the clinical implementation of FLASH radiotherapy: a dose ceiling below 24 Gy to preserve the skin-sparing effect and a dose-rate threshold exceeding 200 Gy/s for efficacy, with further optimization achieved at rates above 250 Gy/s. These findings provide ​guidelines for minimizing radiotherapy-induced acute skin toxicity while maintaining comparable antitumor efficacy, thereby outlining a translatable pathway towards the clinical translation of FLASH-RT.

Background and AimThis study investigated the dose-dependent cardioprotective effects of Pterocarpus indicus extract (P.indicus; LD: 27, MD: 54, HD: 108 mg/kg) against isoproterenol (ISO)-induced myocardial ischemia in rats, focusing on oxidative stress, apoptosis, inflammation, and fibrosis.Experimental procedureRats were pretreated for 14 days and divided into control, ISO, propranolol, and P.indicus (LD, MD, HD) groups. Myocardial injury was assessed via ECG, histopathology, serum biomarkers (CK-MB, LDH, cTnT, IL-6, IL-1β, TNF-α), oxidative markers (SOD, MDA, GSH-Px), and apoptosis-related proteins (Bax, Bcl-2, Caspase-3). Nrf2/HO-1 expression was analyzed by western blot. Phytochemical profiling was performed via UPLC-MS/MS and HPLC. Pharmacokinetics, safety, and therapeutic-regimen efficacy were also evaluated.ResultsP.indicus at MD and HD significantly attenuated ISO-induced ECG abnormalities, histopathological damage, serum injury markers, inflammatory cytokines, and fibrosis (all P < 0.01). Treatment suppressed oxidative stress (restored SOD/GSH-Px, reduced MDA) via Nrf2/HO-1 activation and inhibited apoptosis via Bax/Bcl-2/Caspase-3 modulation. The efficacy of MD (EC50 ∼50 mg/kg) was confirmed by dose-response analysis. Pharmacological inhibition established that both Nrf2 activation and caspase-3 inhibition are necessary for P.indicus’s effects. PK studies showed systemic exposure to key compounds (quercetin-3-O-glucoside, ferulic acid, linoleic acid), and a 14-day safety assessment revealed no hepatorenal toxicity. Post-injury therapeutic administration also conferred significant protection.ConclusionP. indicus extract confers dose-dependent cardioprotection against ISO-induced myocardial injury through dual modulation of the Nrf2/HO-1 and Bax/Bcl-2/Caspase-3 pathways, with the medium dose (54 mg/kg) identified as optimally effective and well-tolerated.

The field of dose-response research has evolved dramatically, propelled by advancements in exposomics concept, multi-omics technologies, and a growing appreciation of low-dose effects across disciplines. This editorial article highlights recent key publications in Dose-Response that reflect these trends and outlines the journal’s renewed commitment to publishing rigorous, innovative research that bridges traditional toxicology with modern systems biology. Meanwhile, this editorial article also addresses the future directions for Dose-Response. Finally, Dose-Response will remain dedicated to advancing the science of biological responsiveness to low-dose stressors. By embracing exposomics, multi-omics, and mechanistic toxicology, we aim to foster interdisciplinary dialogue and translate research into evidence-based policies. Through collaboration with our authors, reviewers, and readers, from global scientific community, we wish and also confident to reach this exciting new chapter.

ObjectivePinus roxburghii Sarg. (Pinaceae) has shown useful effects in the treatment of urinary problems. This research aimed to explore P.roxburghii scientifically via in-vitro, in-vivo and in-silico techniques to find out its therapeutic benefits on kidney and bladder.MethodPharmacologically active components of aqueous ethanolic extract of P.roxburghii were analyzed by HPLC-DAD screening. These components were predicted for multfi-mechanisms and spasmolytic effects in network pharmacology. In-vitro experiments were conducted on isolated bladder of rat to analyze the spasmolytic effects of plant extract. Spasmolytic effects were also compared with the standard drugs verapamil and oxybutynin In-vivo experiments were also performed to observe diuretic and nephroprotective potential of the plant.ResultPhytochemical analysis indicated the presence of chlorogenic acid, gallic acid, P-coumaric acid, kaempferol, salicylic acid, sinapic acid and benzoic acid. Aqueous ethanolic extract of plant relaxed the contractions induced by high K+ (80 mm) and carbachol (1 µM) in isolated urinary bladder strips of rat. In-vivo experiments revealed the nephroprotective and diuretic potential.ConclusionSo it has been proved via scientific evidence that the concerned plant possesses spasmolytic, nephroprotective and diuretic potential and may be an important therapeutic agent against urinary problems in the near future.

[This retracts the article DOI: 10.1177/1559325819891262.].

Objectives: Nalidixic acid has been used as a potent antibiotic drug in the biomedical sciences. In this study, we assessed photochemical properties of nalidixic acid as well as its effect for photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line over the course of 24 h under the ambient UVB intensity.Methods: Reactive oxygen species such as singlet oxygen (1O2), superoxide anion radical (O2•−), and hydroxyl radical (•OH) were measured by photochemical test and photocytotoxicity, apoptosis, and genotoxicity on the mouse fibroblast (L929) cell line were determined by various methods.Results: Furthermore, in UV-B irritated L929 cells, nalidixic acid decreased GSH and raised LPO levels compared to dark control cells. Nalidixic acid caused concentration-dependent toxicological effects (P < 0.05) in L929 cells when exposed to ambient UVB intensity (1.4 mW/cm2). DNA fragmentation and caspase-3 activity were observed to be significantly (P < 0.05) activated in L929 cells under co-exposure of UV-B and nalidixic acid.Conclusion: Our results thus confirm that when exposed to UVB rays, nalidixic acid exhibits both phototoxic and photo-genotoxic effects.

PurposeThis work was the first study to show the impact of γ- radiation on adropin levels in the serum and liver tissue of male albino rats.MethodsLiver tissue and blood samples of rats were collected at 1, 3, 7 and 14 days after whole-body exposure to 7.5 Gy of γ-radiation.ResultsIrradiated groups revealed a marked decrease in adropin associated with a significant increase in STAT3 in the serum and gene expression. Furthermore, lipid profile (cholesterol, T.G, HDL, LDL, VLDL), liver function (AST, ALT, albumin and total protein), complete blood count (RBCs, WBCs, PLT, Hb, Hct%, MCH, MCV, WBCs differential), glucose and insulin were exhibited more noticeable alterations at all time periods of the experiment. In addition, data exhibited an obvious elevation in some inflammatory markers (IL-6) and TOS accompanied by a decline in the TAC.Conclusion and future scope of workγ- radiation has adverse effects on adropin that related inversely with STAT3, leading to further damage to liver cells as well as disturbances in lipid and glucose metabolism. Therefore, adropin could be used in people exposed to radiation such radiotherapy to control the serious effects of radiation. Further study is needed to confirm these results.