Recent Publications

RSC Adv. 2026 May 11;16(27):24378-24399. doi: 10.1039/d6ra01845a. eCollection 2026 May 8.

ABSTRACT

ABX3 perovskite materials have shown great potential for optoelectronic applications in recent years. In this study, first-principles density functional theory (DFT) is used to thoroughly analyze the structural, electronic, thermo-mechanical and photocatalytic properties of lead-free novel cubic halide perovskites GaBX3 (B = Cd, Zn; X = Cl, Br). Structural analysis brought about the thermodynamic stability in the space group Pm3̄m with negative formation enthalpy and decomposition energy. GaZnCl3 was found to have the most stable material with a formation enthalpy of -2.938 eV per atom. Negative decomposition energies confirm the stability of these ternary phases against separation into binary constituents. Electronic band structure calculations, refined with the HSE06 functional, show that the bandgap of these novel materials varies from 0.65-3.37 eV. The optical properties are high absorption coefficients more than 105 cm-1 in the UV and visible regions, as well as a static refractive index between 1.85 and 2.20 increasing with Br substituent. The ductile nature (B/G > 1.75) and satisfying Born Stability Criteria proves mechanical stability. Thermal property analysis, including Debye temperatures up to 240 K, suggests high lattice rigidity and stability in Cl-based systems. Furthermore, the band edge alignments demonstrate that these materials possess the requisite redox potentials for visible light driven water splitting, with valence band maxima (VBM) and conduction band minima (CBM) effectively straddling the water oxidation and reduction potentials. While phonon dispersion curves at 0 K exhibit imaginary frequencies, indicating the cubic phase as a metastable state stabilized by finite-temperature effects. These findings strongly suggest the prospective applications of these novel materials in a wide range of optoelectronic devices.

PMID:42124842 | PMC:PMC13158849 | DOI:10.1039/d6ra01845a

Nat Ecol Evol. 2026 May;10(5):829-832. doi: 10.1038/s41559-026-03064-8.

NO ABSTRACT

PMID:42120946 | DOI:10.1038/s41559-026-03064-8

Animal Model Exp Med. 2026 May 12. doi: 10.1002/ame2.70223. Online ahead of print.

ABSTRACT

Use of animals in biomedical research is still considered essential by many in academia, industry and regulatory authorities. Therefore, it is important that legal, governance and welfare procedures are in place to ensure that only necessary procedures using animals are carried out and that this occurs within a framework with animal welfare at its core. Animal research in the United Kingdom is conducted under the Animals (Scientific Procedures) Act 1986 and animal research in the United Kingdom has long been seen as a flag bearer for high quality-high welfare research. An example of the leading role taken in supporting animal welfare in research was establishment of the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) to support reducing the scale and impact of animal research. Here, we provide an overview of governance and licensing procedures of animal research in the United Kingdom, coupled with explanations of how excellent welfare underpins high quality research, and examine the development of new approach methodologies.

PMID:42117335 | DOI:10.1002/ame2.70223

Alzheimers Dement (Amst). 2026 May 8;18(2):e70295. doi: 10.1002/dad2.70295. eCollection 2026 Apr-Jun.

ABSTRACT

This scoping review explored characteristics and impacts of community-based dementia education programs developed for East and Southeast Asian diaspora, including Chinese, Japanese, Korean, Filipino, and Vietnamese communities. Studies involving community-dwelling adults and people impacted by dementia were identified through several databases. Data on study characteristics, program design, implementation, and impact were extracted. Of the 3431 records screened, 26 met inclusion criteria: 11 targeted general community members and 15 involved caregivers. Only 10 programs engaged individuals living with dementia or caregivers in their development. Community-focused initiatives improved literacy and attitudes, while caregiver-focused programs showed feasibility and preliminary effectiveness in reducing caregiver burden. Most initiatives were at the pilot stage and required cultural tailoring. To address gaps in dementia awareness, stigma, and accessibility, culturally tailored education, developed with meaningful community involvement, will be essential for strengthening dementia care and support within Asian diaspora populations.

PMID:42110324 | PMC:PMC13154145 | DOI:10.1002/dad2.70295

Biosystems. 2026 May 8:105812. doi: 10.1016/j.biosystems.2026.105812. Online ahead of print.

ABSTRACT

Biological systems execute discrete, often irreversible actions - from DNA replication and cell-state transitions to Venus flytrap closure, vertebrate sex change, and human symbolic behavior - not as graded responses to single variables but as threshold-governed events emerging from the convergence of multiple necessary conditions. Here we formalize this convergence logic as the ARCH × Φ framework: a multiplicative threshold function in which Archetype (A, the conserved structural substrate), Drive (D, the energetic or hormonal activation), Context (C, the releasing stimulus or social cue), and Gating Field (Φ, a sterol-modulated permissiveness variable) must jointly exceed a system-specific commitment threshold θ. The multiplicative structure enforces a zero-term veto: suppression of any single component collapses execution regardless of the state of the other three. We trace the physical origin of Φ to the incorporation of sterols into eukaryotic membranes approximately 2.4 billion years ago, at the Great Oxidation Event, when oxygen-dependent sterol biosynthesis first separated stored electrochemical drive from discharge permissiveness - two quantities physically coupled in all pre-sterol membrane systems and independently tunable only with the arrival of the cholesterol ring structure. We propose that Φ is instantiated across three cholesterol-derived tiers: rapid modulation through accessible cholesterol pools and their oxysterol derivatives, intermediate modulation through neurosteroids synthesized via mitochondrial pathways, and lifetime-scale modulation through structural cholesterol deployment in myelin and perineuronal nets - all expressions of a single biophysical mechanism. We extend this account to two additional isoprenoid-based Φ systems: non-photochemical quenching (NPQ) in plant chloroplasts, where zeaxanthin and the PsbS protein constitute a zero-term veto gate for light-energy dissipation that is characterized to picosecond resolution, and insect holometabolous metamorphosis, where juvenile hormone functions as a Φ-suppressor and the dietary sterol auxotrophy of insects produces an environmentally gated Φ architecture distinct from the endogenous sterol synthesis of vertebrates. Monogenic Φ-lock disorders - exemplified by Niemann-Pick type C disease, in which disrupted intracellular cholesterol trafficking abolishes KCNQ2/3-dependent inhibitory gating - provide pathological proof-of-concept for the Φ-lock failure mode at the molecular level. The framework is formally equivalent to the h inactivation variable derived independently by Hodgkin and Huxley from squid axon voltage-clamp data in 1952, implying that Φ is not solely a theoretical construct but a measurable property of excitable membranes with a 2.4-billion-year evolutionary history. Explicit, falsifiable predictions are derived regarding perturbation-matrix experiments, CYP46A1 polymorphism effects on behavioral thresholds, the correlation of sterol enzyme diversity with behavioral plasticity rather than execution speed across taxa, dietary sterol auxotrophy and insect developmental plasticity, and τΦ acceleration as a route to increased biological output yield.

PMID:42107486 | DOI:10.1016/j.biosystems.2026.105812

Sci Rep. 2026 May 9. doi: 10.1038/s41598-026-48128-8. Online ahead of print.

ABSTRACT

This study presents a novel hybrid cryptographic model designed to enhance privacy preservation and data integrity in IoT-enabled Wireless Sensor Networks (WSNs). Traditional algorithms such as RSA, AES, and Blowfish are evaluated and combined into a Hybrid Model to address the resource-constrained nature of IoT devices. The proposed model was tested on a dataset of sensor data, with performance metrics including encryption/decryption time, security strength, memory usage, data throughput, and communication overhead. Numerical findings demonstrate the Hybrid Model's superior performance, with encryption time reduced by 18% compared to Advanced Encryption Standard (AES), The hybrid model employs RSA-2048 (112-bit security strength) for key exchange and AES-256/Blowfish for data encryption (256-bit confidentiality protection). The memory usage was optimized, requiring only 25.16 KB, making it suitable for low-power IoT devices. Additionally, the Hybrid Model achieved a data throughput of 24.89 KB/s and reduced communication overhead to 1.32 KB. These results highlight the efficiency and robustness of the Hybrid Model in securing IoT-enabled WSNs. This research contributes a scalable, resource-efficient solution for privacy and data integrity, offering a promising advancement for real-time IoT applications in sectors such as healthcare, industrial automation, and smart homes.

PMID:42106393 | DOI:10.1038/s41598-026-48128-8

Nat Commun. 2026 May 7. doi: 10.1038/s41467-026-71902-1. Online ahead of print.

ABSTRACT

Apicomplexan parasites like Toxoplasma gondii harbor a divergent mitochondrial proteome, much of which remains uncharacterized despite its essentiality for parasite survival. One such essential pathway is ubiquinone (UQ) biosynthesis. Here, we characterize the UQ synthesis machinery in T. gondii and show that conserved enzymes, TgCoq3 and TgCoq5, are essential for growth and mitochondrial function, and associate in a multi-protein complex. Using proximity labeling and subcellular fractionation, approaches suited to detect low-abundance proteins, we identify TgCoqFMO, a FAD-dependent monooxygenase required for UQ synthesis. Unlike canonical eukaryotic systems that employ multiple monooxygenases to modify specific carbons on the UQ aromatic ring, TgCoqFMO catalyzes two distinct hydroxylation steps, an activity not previously reported in eukaryotes. Molecular docking and chemical screening identified TgCoqFMO inhibitors that impair tachyzoite growth and reduce bradyzoite viability. These findings reveal a divergent UQ biosynthesis pathway with fewer components in apicomplexans and establish TgCoqFMO as a promising antiparasitic target.

PMID:42098088 | DOI:10.1038/s41467-026-71902-1

medRxiv [Preprint]. 2026 Apr 27:2026.04.24.26351712. doi: 10.64898/2026.04.24.26351712.

ABSTRACT

BACKGROUND: Microvascular dysfunction is a key contributor to the development and progression of chronic kidney disease (CKD), yet direct and reproducible assessment of microvascular function in clinical CKD populations remains limited. Laser Doppler flowmetry (LDF) provides a noninvasive, dynamic assessment of skin microvascular blood flow and may serve as a surrogate measure of systemic microvascular health. However, the extent to which LDF-derived measures relate to kidney function, proteinuria, and kidney histopathology in CKD remains unclear.

METHODS: We assessed cutaneous microvascular function in 150 participants with CKD (estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m²) using a standardized forearm LDF protocol. Baseline perfusion was recorded at ∼30°C, followed by local heating to 44 °C to induce hyperemia. The percentage change in perfusion unit (PU) was calculated and used to define microvascular functional reserve. Associations between LDF-derived measures with eGFR and urine protein-to-creatinine ratio (uPCR) were assessed using multivariable linear regression adjusted for demographic and clinical covariates. Unsupervised k-means clustering was performed to identify microvascular phenotypes based on resting PU and microvascular function reserve. Associations of LDF measures with glomerulosclerosis (GS) and interstitial fibrosis and tubular atrophy (IFTA) were evaluated in a subset of participants (n = 20) who underwent clinically indicated kidney biopsies.

RESULTS: Among 150 CKD participants, the mean (SD) age was 64 (14) years, 46% were female, 38% had diabetes, and 83% had hypertension. The mean eGFR was 42 (21) mL/min/1.73 m² and median uPCR was 0.21 (interquartile range (IQR) 0.11 to 1.20) mg/mg. Higher baseline PU (β = -12; 95% CI, -24 to -1) and reduced percentage change in PU (β = 7; 95% CI, 2 to 13) was associated with lower eGFR, independent of covariates. Baseline PU or percentage change in PU were not associated with uPCR. Unsupervised clustering identified four distinct microvascular phenotypes characterized by graded differences in resting perfusion and microvascular function reserve. Among participants with biopsy data, higher baseline PU and lower percentage change in PU were associated with greater severity of GS and IFTA.

CONCLUSION: In persons with CKD, elevated resting perfusion and impaired microvascular functional reserve were associated with lower eGFR. These findings suggest that LDF-derived measures capture clinically relevant alterations in systemic microvascular function and may serve as a noninvasive biomarker of kidney function and underlying histopathologic injury in CKD.

PMID:42094166 | PMC:PMC13142588 | DOI:10.64898/2026.04.24.26351712

Bioengineering (Basel). 2026 Apr 14;13(4):458. doi: 10.3390/bioengineering13040458.

ABSTRACT

Understanding human's responses to extreme environments holds significant importance for space exploration, deep-sea research, and environmental adaptation. Traditionally, human subjects were used to study humans' responses to extreme environments. The main limitations of this approach include the inability to independently investigate specific cellular mechanisms, ethical and safety constraints, limited experimental controllability, and inter-individual variability that complicates mechanistic interpretation. Another approach is to study humans' responses at the cellular level using 2D culture. This approach often exhibits limited reproducibility due to its inability to recapitulate physiologically relevant microenvironments. Bioprinting can enable studies on human's responses at the cellular level and within 3D environments. One way is to study human cells' responses to localized and transient extreme environments created during printing. Another way is to expose 3D printed samples (embedded with human cells) to extreme environments. However, the literature does not contain comprehensive review papers to discuss the prospects and limitations of bioprinting for investigating human cells' responses to extreme environments. This review paper aims to fill this gap in the literature. It begins with a brief description of the effects of extreme environments on human health and summarizes reported studies on cells' responses to extreme environments. Afterward, it discusses the prospects and limitations of the two ways of using bioprinting to investigate cells' responses to extreme environments. Finally, it concludes with identifying knowledge gaps and proposing research directions in the application of bioprinting to study human cells' responses to extreme environments.

PMID:42072252 | DOI:10.3390/bioengineering13040458

Cell Rep. 2026 Apr 30;45(5):117335. doi: 10.1016/j.celrep.2026.117335. Online ahead of print.

ABSTRACT

Protein-based mosaic-8 nanoparticles displaying eight SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) elicited broadly cross-reactive antibodies that could protect from zoonotic spillovers. Here, we extend the mosaic-8 concept to mRNA by encoding membrane-bound RBD quartets (four linked RBDs) as dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, the latter leveraging ESCRT- and ALIX-binding region (EABR) technology for display on cell surfaces and secreted virus-like particles. Compared with protein-based mosaic-8, mRNA-encoded mosaic-8 induced equivalent or enhanced antibody breadth, neutralization potencies, and conserved epitope targeting, while eliciting enhanced T cell responses and more balanced IgG subclass profiles consistent with potentially superior Fc effector functions. Finally, systems serology-polyclonal epitope mapping (SySPEM) revealed distinct IgG-subclass-specific epitope signatures across mRNA, EABR-mRNA, and protein vaccines, demonstrating that the mode of antigen display can shape epitope recognition. Successful conversion of a multivalent protein vaccine to mRNA platforms informs the design of broadly protective vaccines and advances mosaic-8 toward clinical development.

PMID:42068547 | DOI:10.1016/j.celrep.2026.117335

Precis Chem. 2026 Jan 2;4(4):380-387. doi: 10.1021/prechem.5c00320. eCollection 2026 Apr 27.

ABSTRACT

Through an earth-abundant molybdenum-catalyzed, borrowing hydrogen coupling reaction, a simple and efficient synthesis of tetrahydroquinolines from (2-amino aryl) methanol and α-branched alcohols has been reported. The current methodology proceeds via an atom-efficient and step-economic pathway, along with no need for further reducing agent, broad substrate scope, and operational simplicity, providing a practical and important way for the smooth synthesis of these types of biologically relevant products.

PMID:42064193 | PMC:PMC13126386 | DOI:10.1021/prechem.5c00320

Vet Med Sci. 2026 May;12(3):e70965. doi: 10.1002/vms3.70965.

ABSTRACT

BACKGROUND: Eustrongylides (nematode: Dioctophymatidae) are parasitic nematodes of freshwater fishes and fish-eating birds. It has zoonotic potential and poses a threat to human health, as infection can occur through the consumption of raw or undercooked fish.

OBJECTIVES: The present study was designed to characterize Eustrongylides sp. isolated from Channa punctata using the Internal Transcribed Spacer 2 (ITS2) regions.

METHODS: In this study, a total of 137 medium-sized C. punctata (17.5 ± 2.5 cm) were collected from different locations of Jamalpur and Netrokona district, Bangladesh and isolated 44 nematodes. DNA was extracted from the parasites, amplified in the ITS2 region and sequenced.

RESULTS: All the nematodes were microscopically identified as belonging to the genus Eustrongylides based on morphological characteristics, including the presence of inner and outer circle labial papillae at the anterior end and the esophago-intestinal junction. Initially, the sequences were confirmed up to the lowest taxonomic level possible using Basic Local Alignment Search Tool (BLAST). For phylogenetic analysis, reference sequences of Eustrongylides sp. were aligned, and two single nucleotide polymorphisms (SNPs) were detected. The average sequence identity percentage (%) within the studied sequences ranged from 99.7% to 99.8%. A maximum-likelihood (ML) tree was constructed which showed that the studied sequences clustered within the Eustrongylides sp. lineage and grouped with reference sequences, supported by moderate bootstrap values (82%).

CONCLUSIONS: Close genetic similarity was observed when compared with reference sequences of Eustrongylides sp. Further studies on the investigation of genetic pattern of Eustrongylides sp. throughout the country are essential to control this parasite.

PMID:42053999 | DOI:10.1002/vms3.70965

J Chem Inf Model. 2026 Apr 28. doi: 10.1021/acs.jcim.5c02320. Online ahead of print.

ABSTRACT

Dispersion sensor (DspS) is a membrane-bound histidine kinase in Pseudomonas aeruginosa that senses cis-2-decenoic acid (CDA), a fatty acid signal regulating biofilm dispersion, motility, and virulence. However, its structural mechanism of signal transduction remains poorly defined. Here, we combined AlphaFold-Multimer modeling, multiple-replica accelerated molecular dynamics simulations, and Markov state modeling (MSM) to investigate the conformational dynamics of full-length dimeric DspS. Simulations focused on the cyclases/histidine kinase-associated sensory extracellular domain and transmembrane (TM) helices under four conditions: apo, dual-CDA-bound, dual arginine-to-alanine substitution, and single-CDA-bound. The apo form displayed a loosely packed TM2-TM2' helical arrangement, whereas dual CDA binding promoted a tightly crossed, signaling-competent configuration. In contrast, disruption of the conserved Arg residue weakened ligand anchoring and partially destabilized this packing. Under single-CDA binding, the DspS dimer adopted a primed state arising from asymmetrical ligand occupancy. In this state, the dimer bent toward the membrane interface, suggesting a distinct structural rearrangement relative to the apo and dual-bound forms. Such asymmetry may represent a mechanistic adaptation to fluctuating CDA levels, allowing graded receptor activation under dynamic environmental conditions. MSM analysis further revealed conformational plasticity, showing that full ligand occupancy stabilizes a network of metastable states and enables transitions within an active-like conformational ensemble. These findings provide the first atomistic view of DspS conformational switching, establishing a structural framework to study related histidine kinases and design antivirulence strategies targeting DspS-mediated biofilm control.

PMID:42050969 | DOI:10.1021/acs.jcim.5c02320

Commun Biol. 2026 Apr 26. doi: 10.1038/s42003-026-10110-5. Online ahead of print.

ABSTRACT

Cell-based assays are fundamental to G protein-coupled receptor (GPCRs) drug discovery. As the field strives to increase the use of physiological cell types with endogenous receptor expression, enhancing the sensitivity of simple-to-use assays unlocks new screening modalities. Here, we enhanced the responsivity of a Nuclear Factor of Activated T cells response element (NFAT-RE) reporter, by concatenating the IL-2 promoter-derived triplicate-binding sites, to produce three nano-luciferase reporter constructs termed NFAT 2X, NFAT 3X and NFAT 4X. Our enhanced reporters demonstrate larger maximal Fold Induction (FI) when co-expressed with both primarily and secondarily Gαq/11-coupled GPCRs. This pattern was maintained when stimulating endogenous GPCRs in a panel of immortalised cell lines (HEK293, HeLa, A549, and HEK293T) and allowed us to observe Sphingosine-1-Phosphate (S1P)-mediated signalling in primary human CD8+ T cells via CRISPR/Cas9 knock-in. Our NFAT-reporter T cells demonstrate the reporters potential for use in bi-allelic expression systems and primary cell types.

PMID:42034830 | DOI:10.1038/s42003-026-10110-5

BMC Womens Health. 2026 Apr 23. doi: 10.1186/s12905-026-04488-x. Online ahead of print.

NO ABSTRACT

PMID:42026635 | DOI:10.1186/s12905-026-04488-x

Cell Metab. 2026 Apr 22:S1550-4131(26)00111-7. doi: 10.1016/j.cmet.2026.03.017. Online ahead of print.

ABSTRACT

Dietary protein promotes satiety and weight loss, yet how appetite-regulating neurons sense dietary protein remains poorly understood. Here, we show that Cacna1g, which encodes the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates neuronal leucine sensing. Pharmacological inhibition of Cav3.1 blunts leucine-induced activation of pro-opiomelanocortin (POMC) neurons in cultured neurons and brain slices, thereby suppressing the anorectic response to hypothalamic leucine in vivo. Genetic deletion of Cacna1g in POMC neurons abolishes the appetite- and weight-suppressive effects of high-protein feeding. Mechanistically, leucine binds a hydrophobic pocket of Cav3.1 and lowers its threshold for voltage-dependent activation. Finally, pharmacological activation of mediobasal hypothalamic Cav3.1 promotes weight loss in diet-induced obese mice and potentiates responses to anorectic agents, including liraglutide. Together, these findings establish hypothalamic Cav3.1 as a neuronal leucine sensor and nominate it as a tractable target for anti-obesity therapy.

PMID:42025169 | DOI:10.1016/j.cmet.2026.03.017

Indian J Med Res. 2026 Mar;163(3):387-398. doi: 10.25259/IJMR_2866_2025.

ABSTRACT

Background and objectives Despite a high incidence of hypopharyngeal cancer in northeast India, the role of dietary patterns and meal timing remains poorly understood. This study examined the association between inter-meal intervals, dietary patterns, and the risk of hypopharyngeal cancer in northeastern India. Methods A hospital-based case-control study was conducted at a tertiary cancer centre in northeastern India, enrolling 300 histologically confirmed cases with hypopharyngeal cancer and 300 frequency-matched controls between May 2023 and August 2024. Dietary intake and inter-meal intervals were assessed using a semi-quantitative food frequency questionnaire. Multivariable logistic regression calculated odds ratios and 95% confidence intervals, adjusting for demographics, socioeconomic status, alcohol consumption, smoking, and tobacco use, including areca nut consumption. Results Prolonged inter-meal intervals (≥5 h) conferred a nearly three-fold increased risk of hypopharyngeal cancer compared to intervals <4 h [adjusted odds ratio (OR) 2.69, 95% confidence interval (CI): 1.56-4.69]. Strong protective effects emerged for citrus fruits (highest tertile OR 0.13, 95% CI: 0.05-0.32) and leafy green vegetables (highest tertile OR 0.21, 95% CI: 0.09-0.49). Coffee consumption was inversely associated with the risk of hypopharyngeal cancer (OR 0.54, 95% CI: 0.30-0.94), while higher milk intake increased the risk of hypopharyngeal cancer (OR 2.06, 95% CI: 1.22-3.52). Interpretation and conclusions We provide epidemiological evidence linking prolonged inter-meal intervals to the risk of hypopharyngeal carcinoma in an Indian population. Meal timing patterns may be as important as dietary composition for cancer prevention, with implications for public health interventions in high-risk populations.

PMID:42024901 | DOI:10.25259/IJMR_2866_2025

Br J Biomed Sci. 2026 Apr 7;83:15884. doi: 10.3389/bjbs.2026.15884. eCollection 2026.

ABSTRACT

BACKGROUND: The G protein-coupled receptor 68 (GPR68) detects variations in extracellular pH, and has potential roles in homeostasis and responses to ischaemia and inflammation within different organs, including the gastrointestinal tract. However, in the human colon the distribution of GPR68 remains unclear. We examined the localization and density of GPR68 within the ascending (AC) and descending (DC) human colon from younger and older adults.

METHODS: Macroscopically normal AC and DC were obtained from patients undergoing lower bowel cancer resection (aged 22-91 years; grouped into younger (≤60 years) and older (≥67 years) populations). Immunolabelling was performed using formalin-fixed, paraffin-embedded sections and antibodies against GPR68, protein gene product 9.5 (PGP9.5) and calretinin to identify the presence and density of GPR68-immunoreactive (IR) expressing cells.

RESULTS: Ageing did not change the density of total PGP9.5-IR enteric neuronal fibres in the AC or DC. For the myenteric plexus (MP) of both age groups, the densities of calretinin-IR neurons were similar in both the AC (younger: 1.2 ± 0.3 × 10-3; older: 0.9 ± 0.2 × 10-3 per mm2 plexus) and DC (1.4 ± 0.2 × 10-3; 1.3 ± 0.3 × 10-3 per mm2 plexus), but reduced in the mucosa of older adults for both AC (respectively, 9.8 ± 0.5 vs. 3.2 ± 0.1/pixel) and DC (11.5 ± 0.9 vs. 7.4 ± 0.3/pixel). Similar reduction of calretinin-IR enteric neurons was found in the SMP of AC but not clearly in the DC in the older adults. GPR68 was widely expressed in the mucosa, circular muscle and myenteric plexus of both the AC and DC. The density of GPR68-IR in the muscle and myenteric plexus was similar in both age groups, but smaller in the mucosa of older adults for both AC and DC.

CONCLUSION: GPR68 is widely distributed within the enteric nervous system of the human colon, with potential roles for GPR68 suggested in the muscle and MP, and in the functions of calretinin-IR neurons within the mucosa. Further, the concomitant loss of GPR68 and calretinin-IR neurons in the mucosa of older adults suggests selective vulnerability of mucosal sensory and homeostatic mechanisms of the ageing colon.

PMID:42022898 | PMC:PMC13095668 | DOI:10.3389/bjbs.2026.15884

Pain Rep. 2026 Apr 20;11(3):e1446. doi: 10.1097/PR9.0000000000001446. eCollection 2026 Jun.

ABSTRACT

INTRODUCTION: Abdominal pain is a significant burden for those living with inflammatory bowel disease (IBD), representing a major unmet clinical need due to the scarcity of effective therapeutic options. The G protein-coupled receptor, protease-activated receptor 2 (PAR2), has emerged as a promising therapeutic target for visceral pain management in IBD.

OBJECTIVES: We set out to determine signaling mechanisms deployed by PAR2 in the lumbar splanchnic nerve and whether inhibiting PAR2 with the mouse monoclonal antibody (mAb), PAR650097 (mPAR650097) provided therapeutic benefit in dextran sulfate sodium (DSS)-induced colitis.

METHODS: We first used ex vivo electrophysiological recordings of mouse lumbar splanchnic nerve to determine how stimulation of PAR2 alters afferent activity and the intracellular signaling mechanisms involved. Second, we used the DSS model of colitis in mice and determined how mPAR650097 altered disease activity, behavior, colon histology, and the activity of nociceptive circuitry.

RESULTS: Protease-activated receptor 2 stimulation in the colon activated visceral afferent fibers and sensitized them to mechanical and chemical stimuli. We found that endosomal internalization and protein kinase A/C signaling mediate both activating and sensitizing effects of PAR2 in visceral pain. We further show that inhibiting PAR2 with the mAb mPAR650097 reduces DSS-induced colitis severity and pain. mPAR650097 also reduced several colitis-induced pain correlates at key points along the pain-signaling axis, including peripheral nociceptive neuron signaling and sensitivity, expression of proinflammatory mediators, spinal cord signaling, and, fundamentally, behavior.

CONCLUSION: These findings illustrate that mAb inhibition of PAR2 represents a promising approach to provide relief from abdominal pain in those living with IBD.

PMID:42021789 | PMC:PMC13098787 | DOI:10.1097/PR9.0000000000001446

Gastroenterology. 2026 Apr 20:S0016-5085(26)00348-3. doi: 10.1053/j.gastro.2026.03.026. Online ahead of print.

NO ABSTRACT

PMID:42019767 | DOI:10.1053/j.gastro.2026.03.026