Hypoparathyroidism(HypoPT) is rare, and real-world studies of biochemical control in affected patients are limited. This study aimed to analyze biochemical control in a large cohort of patients with adult-onset chronic HypoPT. Subjects were selected from outpatients followed at our center from June 2009 to March 2023. Proportion of measurements in/above/below the target range (MIR/MAR/MBR) and estimated time in/above/below the target range (TIR/TAR/TBR) were calculated. A total of 114 post-surgical (PS-HP) and 64 non-surgical (NS-HP) patients were enrolled, with a median follow-up of 82.5(45.0,108.0) months. The MIR/TIR were 70∼80% for serum calcium (Ca), around 40% for serum phosphorus(P), 80∼90% for 24-hour urine calcium(24hUCa), nearly 100% for calcium-phosphate products, 50∼64% for combined index 1(serum Ca and 24hUCa), and 20∼25% for combined index 2(all four indices). A total of 21 episodes of hypercalcemia occurred in 7 (3.93%) patients among the total 3455 measurements (0.61%). Compared to PS-HP patients, NS-HP patients showed poorer control of serum P, 24hUCa and combined indices. Serum Ca at diagnosis was positively associated with serum Ca TIR (β=21.15, P<0.05). Calcitriol dosage recorded at the last follow-up was negatively associated with TIR of serum Ca (β=-35.30, P<0.01) and 24hUCa (β = -66.19, P < 0.05). Hydrochlorothiazide use recorded at the last follow-up was associated with a 20.99% lower 24hUCa TIR (P < 0.001). Male patients showed higher serum P TIR than female (β1=28.14, P<0.001; β2=16.96, P<0.05). The control of serum Ca and 24hUCa was acceptable, whereas serum P and overall indices were suboptimal in our center. NS-HP patients showed poorer biochemical control than PS-HP patients and need more attention.

Assisted reproductive technology (ART) has been associated with increased cardiovascular risk in offspring, but the underlying mechanisms remain unclear. This study investigated whether alterations in the cardiac renin-angiotensin system (RAS) are associated with increased susceptibility to myocardial fibrosis in offspring conceived via in vitro fertilization (IVF). Bioinformatics analysis and in vivo experiments were integrated. Cardiac transcriptomic data from IVF offspring (GSE211597) were analyzed to identify differentially expressed genes (DEGs), followed by enrichment and protein-protein interaction (PPI) analyses. An IVF mouse model was established and subjected to a high-fat diet (HFD) as "a second hit". Metabolic parameters, cardiac histology, and expression of RAS- and fibrosis-related molecules were assessed. The angiotensin II type 1 receptor (AT1R) antagonist Candesartan was used to evaluate the functional involvement of RAS signaling. Transcriptomic analysis revealed significant alterations in metabolic and extracellular matrix (ECM)-related pathways, with Agt identified as a central hub gene. Under HFD, IVF offspring exhibited aggravated metabolic dysfunction and increased myocardial collagen deposition. Increased expression of angiotensinogen (AGT), AT1R, collagen type I alpha 1 chain (COL1A1), and collagen type I alpha 2 chain (COL1A2) suggested alterations in cardiac RAS signaling accompanied by extracellular matrix (ECM) remodeling. Candesartan partially improved metabolic abnormalities and attenuated RAS- and fibrosis-related molecular changes. IVF is associated with increased susceptibility to cardiac ECM remodeling under metabolic stress, accompanied by alterations in cardiac RAS-related signaling. Pharmacological blockade of AT1R partially attenuated these changes, suggesting a functional contribution of RAS signaling. These findings provide mechanistic insight into developmental origins of health and disease (DOHaD)-related cardiovascular risk and suggest that RAS signaling may represent a potential therapeutic target.

Background/Objectives: Metabolic syndrome (MS) encompasses a cluster of disorders that significantly increase cardiovascular risk. While α-amyrin exhibits antioxidant and anti-inflammatory properties, its poor aqueous solubility and low oral bioavailability hinder its clinical use. This study evaluated the cardioprotective effects of α-amyrin-loaded polymeric nanocapsules (NCαA) in spontaneously hypertensive rats (SHR) with sucrose-induced MS. Methods: First, NCαA was prepared via interfacial deposition of a preformed polymer following organic solvent displacement. The formulation was characterized for particle size, zeta potential, morphology, encapsulation efficiency, and storage stability. Spontaneously hypertensive rats (SHR) received 20% sucrose for 8 weeks and were treated daily by oral gavage for 28 days with NCαA (0.1, 0.3, or 1 mg/kg), unformulated α-amyrin (1 mg/kg), hydrochlorothiazide (25 mg/kg), vehicle, or blank nanocapsules. Cardiovascular, electrocardiographic, echocardiographic, vascular, renal, and biochemical parameters were subsequently assessed. Results: Polymeric NCαA showed spherical and uniform morphology (195.10 ± 1.55 nm; PDI: 0.144; zeta potential: -52.60 mV), 85.85% encapsulation efficiency, efficient sustained release, and 90-day shelf-life stability. In vivo, MS control rats exhibited significant weight gain, hypertension, increased S-wave negative deflection depth, reduced ejection fraction, impaired acetylcholine-mediated vasodilation, depressed serum nitrite, and elevated malondialdehyde. Treatment with NCαA (particularly at 0.3 and 1 mg/kg), unlike unformulated α-amyrin, prevented excessive weight gain, normalized blood pressure, reversed electrophysiological/echocardiographic markers of cardiac overload, restored nitric oxide bioavailability, attenuated lipid peroxidation, and maintained renal hydroelectrolytic balance. Conclusions: Polymeric nanoencapsulation yielded stable nanocapsules with high sustained release, overcoming the biopharmaceutical limitations of α-amyrin. NCαA provides comprehensive cardioprotection against MS-induced damage, representing a promising multi-target strategy for cardiometabolic disorders.

Background: Many widely used drugs-including non-steroidal anti-inflammatory drugs, tetracyclines and thiazide diuretics-are labelled as photosensitising, yet their phototoxicity has been defined almost entirely by ultraviolet A (UVA) exposure. Whether this risk extends to the near-infrared (NIR) wavelengths of lasers commonly used in aesthetic medicine is unclear, and a history of such medication is often treated as a relative contraindication to laser procedures. Methods: A bibliometric analysis of 391 Scopus-indexed publications using VOSviewer was performed to quantitatively map the thematic structure of the retrieved literature. The bibliometric mapping was complemented by sequential refinement of the Scopus corpus and a focused assessment of the final records to determine whether studies directly addressing the predefined experimental question could be identified. We assessed whether 980 nm diode-laser irradiation of normal human dermal fibroblasts (HDFs) induces phototoxicity in the presence of seven photosensitisers (ketoprofen, meloxicam, hydrochlorothiazide, doxycycline and diclofenac, with chlorpromazine and 8-methoxypsoralen as reference photosensitizers). Cells were irradiated through the closed culture-plate lid at two fluences (62.3 and 34.4 mJ/cm and viability was measured 0.5, 1 and 24 h later. Data were analysed by two-way ANOVA (compound × laser), pairwise Welch tests with Benjamini-Hochberg correction, and equivalence testing against an ISO 10993-5-based margin. Results: Viability remained between 82.7% and 109.6% of control under all conditions and never fell below the 70% cytotoxicity threshold. The compound × laser interaction was non-significant at every time point (p = 0.25-0.69), indicating no drug-specific phototoxicity, and no pairwise comparison remained significant after correction. A small, drug- and fluence-independent reduction of about six percentage points was observed but stayed well within the non-cytotoxic range and was equally present in drug-free controls. Conclusions: Under the specific 980 nm irradiation conditions tested, the photosensitising drugs did not increase phototoxicity in normal human dermal fibroblasts. These findings support a wavelength-specific view of drug photosafety: rigorous UVA-directed photoprotection remains essential, whereas the tested drugs did not increase phototoxicity under the specific in vitro 980 nm irradiation conditions evaluated in this study.

Neuroinflammation and oxidative stress are involved in neuropathologies related to learning and memory decline. Angiotensin II contributes to neuroinflammation through angiotensin II type 1 receptors (AT1-R), leading to oxidative stress and release of pro-inflammatory mediators. This study aimed to evaluate the role of brain angiotensin II, via AT1-R, in streptozotocin-induced cognitive decline and neuroinflammation. For this purpose, male Wistar rats were treated with the AT1-R blocker candesartan cilexetil (3 mg/kg) for 25 days. On days 12 and 14, the animals received an intraventricular injection of streptozotocin (3 mg/kg) each day. On day 25, they were tested for spatial, working, and declarative memory through the Morris water maze, holeboard, and novel object recognition tests, respectively. The oxidative stress marker, malondialdehyde, was measured in isolated brain microvessels. Cerebrospinal fluid was collected for tumor necrosis factor-α determination. The volume of the lateral ventricles was evaluated for morphological changes. The AT1-R blocker pretreatment prevented streptozotocin-induced declines in declarative and working memory. No changes in spatial and long-term memory were observed. Streptozotocin increased malondialdehyde in isolated microvessels and tumor necrosis factor-α levels, which were prevented by candesartan administration. All these findings are consistent with the involvement of AT1-R in early streptozotocin-induced changes, with behavioral and inflammatory/morphological outcomes likely mediated by overlapping yet partially distinct mechanisms.

Elevated blood pressure (BP) is the leading cause of cardiovascular disease and a major contributor to mortality, affecting almost one third of the adult population worldwide. Despite strong scientific evidence, guidelines and multiple therapeutic options, many patients remain undertreated or uncontrolled, largely due to poor medication adherence and medical inertia. Complexity of multi-pill regimens contributes significantly to non-adherence, whereas single-pill combinations (SPCs) improve adherence and persistence, accelerate BP control, and promote better long-term outcomes than multiple combinations. Appropriate selection of SPC in individual hypertensive patients may be a difficult though very important task for physicians. Thus, development of tools that may facilitate use of SPC in clinical practice is desirable. Among renin-angiotensin system blockers, olmesartan (OM) has demonstrated sustained efficacy, favourable tolerability, both as monotherapy and in SPCs with amlodipine and/or hydrochlorothiazide, which are available in multiple dosages. The present OM-based platform builds on earlier frameworks and incorporates guidelines' updates complemented by a systematic review of available literature. This "3.0" proposal expands patient categorization to include comorbidities or complications often overlooked in clinical practice guidelines, providing a practical, evidence-based approach to support individualized hypertension management complementing guideline recommendations.

N-nitrosamine drug substance related impurities (NDSRIs) are considered to be within the "cohort of concern" (CoC) due to their potential mutagenic carcinogenicity. However, increasing evidence indicates variability in mutagenic potency across this class. N-nitroso-hydrochlorothiazide (N-nitroso-HCTZ), an impurity associated with hydrochlorothiazide, has shown positive results in bacterial mutagenicity (Ames) assays, although mechanistic studies suggest these findings are likely driven by reactive degradation products rather than the parent compound. To further characterize mutagenic potential in vivo, a transgenic rodent (TGR) gene mutation assay was conducted in the Muta™Mouse test system. Male mice were administered N-nitroso-HCTZ by oral gavage at 0, 18.5, 55.7, 167, 500, or 750 mg/kg/day for 28 consecutive days. Mutant frequency (lacZ) was evaluated in liver and glandular stomach at 167, 500, and 750 mg/kg/day. Systemic exposure was confirmed in a toxicokinetic study following a single 750 mg/kg dose. N-nitroso-HCTZ was well tolerated, and no statistically significant increases in mutant frequency were observed in either tissue at any evaluated dose. All values were within historical control ranges, while the positive control demonstrated the anticipated response. Under the conditions of this study, N-nitroso-HCTZ did not induce gene mutations in vivo.

The renin angiotensin aldosterone system (RAS) regulates blood pressure and fluid balance by a cascade of angiotensin (Ang) peptides. Antihypertensive drug classes differentially modulate this cascade. This study examined how four mechanistically distinct antihypertensive drugs affect plasma concentrations of 10 Ang peptides and aldosterone in untreated hypertensive patients. In this randomized, open-label, parallel-group study, 88 patients received 4 weeks of monotherapy with angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), or hydrochlorothiazide (HCT). Equilibrium concentrations of 10 Ang peptides and aldosterone were quantified by LC-MS at baseline and after 4 weeks, both pre- and 4 h post-dose; drug exposure was confirmed by measured drug concentrations. Seventy-two participants completed the 4-week treatment (ACEi n = 18, ARB n = 17, CCB n = 20, HCT n = 17). The most prominent effects were seen for Ang I, Ang II, and aldosterone and were reflected in biomarkers for plasma renin activity (PRA-Q; Ang I+Ang II), ACE activity (ACE-Q; Ang II/Ang I), and the aldosterone/Ang II ratio (AA2-R). Downstream peptides showed minimal or no changes. Relative to baseline, ACEi increased Ang I and reduced ACE-Q. ARB increased Ang I and Ang II and lowered AA2-R without altering ACE-Q. CCB and HCT produced only minor changes. ACE-Q < 1.05 pM/pM identified ACEi use, and AA2-R < 0.85 pM/pM as well as Ang II > 175 pM identified ARB use. RAS-targeted monotherapy produces distinct peptide-level signatures that can be captured by Ang-derived biomarkers, supporting their potential utility for monitoring drug intake in personalized hypertension management.

Migraine is a common disabling disorder, and optimising affordable preventive treatments remains highly relevant. Candesartan is an effective and well-tolerated preventive treatment, but little is known about its dose-concentration-response relationships. We explored these relationships using data from the MigriNor study, a prospective observational cohort of adults with episodic or chronic migraine initiating oral preventive treatment. A total of 166 participants using candesartan were included (median age 35 years; 89% female). Participants completed a daily electronic headache diary during a 4-week baseline and 12-week follow-up period with accompanying blood sampling. Dosing regimen was flexible. No differences in adverse drug reactions (ADRs) or treatment acceptability were observed between participants starting 4 versus 8 mg. Substantial interindividual variability in serum concentrations was observed. Higher serum concentrations were associated with lower odds of headache attacks (OR = 0.97, 95% CI = 0.96-0.98, p < 0.001) and migraine attacks (OR = 0.98, 95% CI = 0.97-0.99, p = 0.005). Interquartile ranges of serum concentrations among ≥ 30% and ≥ 50% responders were 62.9-141.2 and 62.3-129.3 nmol/L, respectively, suggesting preliminary therapeutic reference ranges. Serum concentration was not associated with ADRs or treatment acceptability. Interpretation is limited by the flexible dosing design, and studies with fixed dosing regimens are warranted.