Lassa fever is a viral haemorrhagic fever that poses a persistent public health threat in several West African countries, particularly Nigeria. The scarcity of Lassa virus (LASV) sequences isolated from small mammal reservoirs limits our knowledge and understanding of LASV genomic diversity and transmission dynamics. To address this knowledge gap, we sampled 1189 small mammals, including mice, rats, and shrews, from two LASV-endemic states in southern Nigeria (Ondo and Ebonyi States) and tested them for the presence of LASV RNA using reverse transcription-quantitative polymerase chain reaction. Selected quantitative polymerase chain reaction-positive samples were subjected to whole genome sequencing and small mammal speciation through next-generation sequencing outputs. We recorded an overall polymerase chain reaction positivity rate of 61.6%, with rat species demonstrating the highest LASV prevalence. We also conducted a serosurvey of 269 small rodents using indirect Enzyme-Linked Immunosorbent Assay (ELISA) and obtained an overall anti-LASV seroprevalence of 45%. Using the Nextera XT metagenomic sequencing protocol, we produced 55 LASV partial (n = 28) and full-length genomes (n = 27) from small mammals sampled, all of which clustered within sublineage 2g. LASV sequences generated from this study suggest that LASV variation is mostly driven by location, as isolates from this study tend to cluster more closely with other isolates collected from within the same region, rather than by collection date or host. However, samples collected from Ebonyi State were more closely related to isolates collected in Ondo State than to isolates from Edo, despite a larger physical distance. Overall, the data from this study suggest free movement of the virus across states in Nigeria, among humans and various non-human taxa. The finding of LASV in additional small mammal hosts suggests that the virus reservoir is vast and may include many small mammals not well-characterized.
Species occupying small habitat patches and exhibiting behavioral and ecological flexibility are more likely to persist in fragmented landscapes. However, when isolated populations are not self-sustaining in the long term, translocation may be required, making an understanding of their behavior critical. Howler monkeys (Alouatta spp.) show high tolerance to habitat restriction, which has been linked to a highly folivorous diet and the exploitation of non-tree plant and non-native species as food sources. We assessed how the size of the habitat patch influences home range size, day range, time spent feeding, young leaf and fruit consumption, and diet richness, the relationships between these behaviors, and the effect of group size and study length on them using Generalized Linear Mixed Models and full model averaging based on a dataset of 97 studies conducted at 62 locations on the behavior of 124 groups representing nine species. Habitat patch size predicted home range size, which showed a positive effect on fruit consumption. Diet richness increased with increasing mean day range. No variable predicted day range, feeding time, and young leaf consumption. The limited and uncertain predictive power of habitat patch size for most variables reflect the unpredictability of the behavioral and ecological responses of howler monkeys to varying conditions of habitat quality. Our findings are consistent with the possibility that the behavioral flexibility enabling howler groups to survive in small, isolated, low quality habitat patches could enhance their value in metapopulation management strategies aimed at promoting long-term persistence of the species in human-modified landscapes.
Gastrointestinal nematodes (GINs) significantly limit small ruminant production in Southern Africa, causing substantial economic losses and reduced livestock productivity. Control largely depends on anthelmintic drugs, but intensive and improper use has accelerated the development of anthelmintic resistance (AHR). This review synthesizes published evidence on AHR in GINs of sheep and goats across Southern Africa, drawing on studies from six countries, and summarizes resistant parasite species, drug classes, diagnostic methods, and associated risk factors. Comparative analyses showed a significant association between anthelmintic class and the proportion of farms exhibiting resistance (P < 0.05). Macrocyclic lactone (ML) resistance, particularly to ivermectin, was most prevalent, with significantly more farms harbouring resistant GIN populations than susceptible ones (P < 0.05). In contrast, the proportions of farms showing resistance to benzimidazoles (BZ) and imidazothiazoles (IMD) did not differ significantly from those with susceptible populations, reflecting variability in resistance patterns at farm level. Salicylanilide compounds exhibited significantly lower resistance prevalence (P < 0.05). Haemonchus spp. was the dominant resistant genus, with 62.2% of farms reporting resistant populations, significantly exceeding those retaining susceptibility (P < 0.05). In contrast, lower resistance levels were observed in Teladorsagia, Trichostrongylus, Oesophagostomum, and Cooperia species. These findings indicate growing evidence of resistance to BZ, ML, and IMD compounds in GINs of small ruminants in Southern Africa. The underlying reasons are unclear but are likely driven by frequent whole-flock treatments, improper dosing, limited drug rotation, reduced refugia, cross-border livestock trade, communal grazing, and non-prescription use of anthelmintics.
Small size imposes constraints on flight due to a reduction in aerodynamic efficiency of small wings. Consequently, miniature insects are often considered to be poor flyers that disperse by drifting in winds. Only few studies have actually measured the active flight of very small insects. The few that did, report surprisingly high flight speeds compared to the size of such small creatures. To test both the limits to flight performance and response to wind, we tracked free-flight within a wind tunnel in a whitefly, a thrips, and a bark beetle. The studied species represent small insects from three different orders (Hemiptera, Thysanoptera and Coleoptera) that underwent independent miniaturization in the course of evolution. Flights were tracked with and without wind and the wind was either horizontal or vertical. From the 3D flight trajectories of the insects, we extracted aerial velocity and manoeuvring performance. The insects did not passively drift downwind and two of the three insects studied displayed distinct upwind flight behaviours. Maximal flight speed was slower than that of larger insects, but faster in terms of body length per second. The manoeuvrability of two out of the three studied species exceeded that of larger animals in terms of flight speed for a minimal turning radius. These findings advocate the inclusion of active flight in small insect dispersal models and suggest that miniaturization may result in improved aerial manoeuvrability.
Fasting enhances small intestinal regeneration after radiation, but the contribution of the gut microbiome to this process remains uncharacterized. We identify Akkermansia muciniphila (AKK) as a key mediator of this response. AKK was enriched in fasted mice and its antibiotic depletion abrogated radioprotection, whereas reintroduction restored both organismal survival and intestinal integrity. Fasting elevated propionic acid, consistent with AKK's metabolic output. AKK-conditioned medium and propionate induced histone H3 acetylation in intestinal stem cell cultures while in vivo fasting induced AKK-dependent H3K27ac and H3K9ac, remodeling promoter-enhancer landscapes in crypt epithelial cells. Epigenetic profiling revealed a rewired core regulatory program enriched for pioneer transcription factors (Foxa, Gata, Klf), architectural organizers (Ctcf, Boris), and lineage-defining and metabolic regulators (Cdx2, Hnf4). This program supports expansion of a population of primed persister cells characterized by open chromatin accessibility at key stem and regenerative-associated loci including Clu, Olfm4, Lgr5, Ascl2, Lrig1, Sox9, Rnf43, and Axin2. These findings define a fasting-induced microbiome-metabolite-chromatin axis that epigenetically primes highly plastic persister cells for rapid regeneration of the intestinal epithelium following radiation-induced injury.
This study delves into the regulatory mechanism of TRERNA1 in ferroptosis of non-small cell lung cancer (NSCLC) cells. TRERNA1, KAT6A, and PIK3CA are abundantly expressed in NSCLC tissues and cells. TRERNA1 is negatively correlated with ACSL4 but positively correlated with GPX4. TRERNA1 knockdown inhibits cell proliferation and promotes ferroptosis. Mechanistically, TRERNA1 interacts with KAT6A protein to promote KAT6A expression and nuclear ectopy. KAT6A acetylates H3K23, which in turn enhances the binding of TRIM24 to H3K23ac. Therefore, TRIM24 acts as a transcriptional activator to activate the transcription of PIK3CA and inhibit ferroptosis. Overexpression of KAT6A or PIK3CA alleviateS the promoting effect of TRERNA1 knockdown on ferroptosis of NSCLC cells. In conclusion, TRERNA1 represses ferroptosis in NSCLC via the KAT6A/H3K23ac/TRIM24-PIK3CA pathway, representing a promising therapeutic strategy for NSCLC.
The health of dairy goat herds may be compromised by infections caused by small ruminant lentiviruses (SRLV) and Mycoplasma agalactiae, particularly under coinfection conditions. This study investigated a dairy goat herd composed of 38 animals with a history of joint enlargement and reduced milk production in Northeastern Brazil. Clinical, serological, molecular, and phylogenetic analyses were performed using blood, milk, synovial fluid, and ocular swab samples. Clinically, arthritis was observed in 28.9% (11/38) of the animals, keratoconjunctivitis in 28.9% (11/38), and mastitis or agalactia in 19.4% (6/31) of the lactating females. For SRLV diagnosis, positivity rates were 31.6% (12/38) by agar gel immunodiffusion (AGID) and 65.8% (25/38) by indirect ELISA, with moderate agreement between tests (K = 0.387; P = 0.002). Indirect ELISA for Mycoplasma spp. detected antibodies in 34.2% (13/38) of the animals, while PCR identified M. agalactiae in 83.3% (5/6) of synovial fluid samples, 66.7% (2/3) of ocular swabs, and 79.3% (23/29) of milk samples. Concomitant clinical manifestations were observed exclusively in coinfected animals. Phylogenetic analysis based on the 16 S rRNA gene supported the molecular identification of M. agalactiae. These findings demonstrate the concomitant circulation of SRLV and M. agalactiae in the investigated herd and reinforce the importance of combining clinical evaluation with serological and molecular methods applied to different biological samples for the diagnosis of coinfections in goats.
The disease-modifying antibody lecanemab for treating Alzheimer's disease (AD) was initially designed to target amyloid-beta (Aβ) protofibrils, i.e. soluble aggregates of Aβ, but it has also been successful in clearing insoluble amyloid plaques in clinical studies. Therefore, this study aimed to investigate how a brain penetrating, bispecific murine variant of lecanemab (RmAb158-scFv8D3) distributes in the brain and interacts with different pools of aggregated Aβ in APP transgenic mice. The alpha-synuclein targeting antibody RmAbSynO2-scFv8D3 was used as control. Further, by performing in vivo high cut-off microdialysis in freely moving animals, brain interstitial fluid (ISF) was continuously collected across 24 h to assess concentrations of free antibody in the brain. Post mortem distribution of the antibodies was analyzed by sequential extraction of brain tissue. RmAb158-scFv8D3 showed rapid ISF clearance as well as a redistribution from brain extracts containing small, soluble Aβ species toward brain extracts containing insoluble, plaque-associated Aβ with time. A treatment effect was detected already at 12 h post injection, whereby the RmAb158-scFv8D3-treated animals showed lower concentrations of the smallest, most soluble Aβ aggregates. Collectively, these findings suggest that within the first 24 h after a single injection of the bispecific RmAb158-scFv8D3 antibody we can capture the antibody's initial brain distribution and interactions with both soluble Aβ aggregates and insoluble, plaque-associated Aβ. These interactions mediate a swift reduction of soluble Aβ, while clearance of insoluble Aβ requires longer treatment time.
Gastrointestinal nematode infections are a common burden in farm animals. As the prevalence of anthelmintic resistance is rising, vaccination is considered a promising alternative for preventive anthelmintic treatments. In search of a vaccine candidate against the bovine small-intestinal helminth Cooperia oncophora, a mid-molecular weight protein fraction (MMW) was isolated from C. oncophora excretory-secretory (ES) material and was protective in a vaccination-infection model. Consequently, the most abundant MMW protein, i.e. a single domain activation-associated secreted protein (Co-sdASP), was purified and evaluated in two vaccine trials, first in a three-dose (initial dose + two repeats) and subsequently in a two-dose (initial dose + one repeat) regimen. The three-dose regimen with native Co-sdASP resulted in 86% reduction in parasite egg output and 63% reduction in worm burden following challenge infection, while the two-dose regimen reduced egg output by 64% but did not significantly affect worm burden. Analyses of immune responses in both vaccination regimens showed that CD4 + T cells and B cells of vaccinated animals exhibited significantly higher proliferation in response to ex vivo restimulation with vaccine antigen, compared to cells from the control groups. In conclusion, Co-sdASP is a promising antigen for vaccinating cattle against C. oncophora infections.
Captive cervid facilities are at elevated risk for chronic wasting disease (CWD) due to high deer densities, close animal contact, environmental contamination, and frequent movement of deer between facilities and across regions. Once CWD becomes established, it spreads quickly and is nearly impossible to eliminate, making early detection critical. However, surveillance in captive herds is challenging: testing only a small portion of the herd during the early stages of CWD outbreak provides a low likelihood of detecting infected deer. Moreover, not detecting CWD in a small sample cannot be interpreted as proof that the facility is free of CWD unless the entire herd is tested using a diagnostic test with 100% sensitivity. We developed a simulation-based approach to interpret surveillance results when CWD is not detected in the sampled subset of animals within captive cervid facilities. This simulation-based approach is retrospective in nature. By integrating deer demographic data, individual movement histories, and past CWD testing records, this tool estimates facility-level CWD detection probabilities, providing a clearer assessment of the likelihood of undetected disease within a facility. Using data from 23 captive cervid facilities in Texas, we demonstrate how this tool can support risk-based monitoring and help wildlife agencies prioritize surveillance and management efforts where they are most needed.
Predator-prey interactions are a major selective force shaping kinematic performance, driving the evolution of extreme speed and power in animal movements1. Small animals such as mantis shrimps, trap-jaw ants and slingshot spiders achieve some of the fastest biological movements to capture prey by using latch-mediated spring actuation mechanisms that produce power outputs several orders of magnitude greater than muscle alone2,3,4. These known power-amplified systems are actively controlled by the predator and act on non-specific prey. Here, we report a unique spring-actuated snare in the Australian ballista spider Propostira sp. that is selectively triggered by the defensive behavior of a specific prey - the green tree ant, Oecophylla smaragdina. We argue that the prey specialization of the ballista spider has driven the evolution of exceptional snare performance. VIDEO ABSTRACT.
How can social animals divide labor to forage effectively without a leader? Effective foraging requires balancing individual exploration costs against collective information gains, but without central coordination. This balance must emerge from the distributed decisions of group members. We address this challenge using a collective foraging model in which individuals share information and rewards but each must choose whether to bear the cost of exploring or to remain idle. We show that decentralized collectives can match the performance of centrally controlled groups through a division of labor with a small exploratory minority bearing the cost of foraging in lean times, continuously gathering information to enable a synchronized majority to exploit favorable conditions. This division of labor is inherently adaptive because fixed individual thresholds produce flexible collective behavior without central adjustment of roles. Information redundancy causes the optimal number of explorers to grow logarithmically with group size, so larger groups need proportionally fewer explorers. We find that the ideal level of group heterogeneity is maximized at intermediate ecological pressures, whereas optimal groups are homogeneous under extreme conditions. Collective responses to environmental changes are asymmetric and detecting improving conditions is slower than detecting deteriorating ones, as the exploratory minority needed to signal recovery is costly to maintain. We thus show how a division of labor based on simple individual threshold rules leads to optimal collective performance without central coordination, and predict when ecological pressures favor heterogeneous vs. uniform group composition.
Peganum harmala L. is a plant rich in β-carboline alkaloids, especially harmine, which is widely used in folk medicine and has therapeutic and toxic effects depending on the dose. In order to determine the toxic properties of harmine, the experiment was carried out by perorally treating this substance to the animals at a dose of 20 mg/kg every day for 14 days. As a result, although the absolute liver weight was significantly increased in the harmine-treated group compared to the control rats (4.65 g vs. 4.25 g, p = 0.04), the relative liver weight was significantly decreased (2.96% vs. 3.55%, p = 0.0045), likely reflecting the disproportionate increase in total body mass observed in the harmine group (157.25 g vs. 119.5 g, p = 0.0002). Additionally, the relative weight of the cerebral hemispheres was significantly reduced, and a statistically significant increase in ALT levels was observed. In the rats treated with harmine, blood was observed in the urine in 85.72% on the first day, and nitrites and proteins were observed in 71.3%. Examination of the amounts of alkaloids in organs and samples, very high amounts of harmine were found, especially in the liver. The 97.78% decrease in harmine content when passing from the stomach to the small intestine indicates its absorption from the stomach. As the result of light and transmission electron microscopy pathological changes were detected due to harmine such as damage to the wall of the central venous vessels and sinusoids, increase in the amount of edema fluid as a result of increased vascular permeability, indistinguishability of boundaries between hepatocytes and steatosis in their cytoplasm, vacuolization, increase in the amount of lysosomes, dystrophy of some nuclei, destruction of the microvilles of bile capillaries.
The activation of stimulator of interferon genes (STING) for the treatment of cancer is a long-standing therapeutic goal. However, the clinical use of orthosteric STING agonists has shown limited utility in patients with advanced/metastatic cancer. C92 is a potent representative of a first-in-class chemical series of allosteric small-molecule human STING agonists that are distinguished by their binding site which lies within STING's proton channel and their consequently unique functional properties. This study characterizes the pharmacology and the anticancer efficacy of C92. Allosteric binding was established using radioligand binding assays. Type I interferon (IFN)-mediated immune signaling due to the activation of STING by C92 was studied in human and murine primary cells. IFN independent actions of C92 were assessed by monitoring inflammasome and autophagy markers in the human monocytic THP-1 cell line. Anticancer activity of CRD3874-SI by the intravenous route as a single agent or in combination with checkpoint inhibitors (CPIs) was evaluated in human STING knock-in C57BL/6 mice. The comparative effects of activating STING in either tumor fibroblasts or non-tumor host tissue were studied in human STING-expressing murine cells that were implanted in wt C57BL/6 and BALB/c mice. C92 is an allosteric agonist that activates STING in the absence of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). In addition, C92 can also potentiate the binding of cGAMP to STING. The allosteric binding site lies within a hydrophobic transmembrane proton channel formed by intertwined helices of two STING monomers. C92 generates strong Type I IFN responses, but without IFN-independent actions such as autophagy and inflammasome formation. Intravenous, oral or intratumoral administration of C92 as a single agent led to robust antitumor immune responses and synergized with CPI treatment providing a path for the clinical translation of C92. The unique species selectivity profile of C92 enabled a demonstration that anticancer effects can be mediated by STING either in tumor cells or in non-tumor host cells. The allosteric small-molecule human STING agonist C92 that blocks STING's proton channel is significantly differentiated from orthosteric STING agonists by its unique pharmacology making it a promising immune therapeutic for the treatment of cancer.
Preclinical migraine research relies on a number of experimental triggers and behavioral assays, often applied under heterogeneous conditions that hinder direct comparison across studies. In addition, small effect sizes frequently require large group sizes, reducing feasibility for pharmacological screening and conflicting with the 3Rs (Replace, Reduce, Refine) principle. Here, we performed a systematic and parallel comparison of two widely used migraine triggers, glyceryl trinitrate (GTN) and calcitonin gene-related peptide (CGRP), across sex and strain in mice. Male and female CD-1 and C57BL/6 J mice were assessed using three commonly employed migraine-relevant readouts: periorbital mechanical allodynia (PMA), light aversion, and facial grimace scoring. All behavioral assessments were conducted sequentially in the same animals using a standardized protocol, with effect sizes deliberately set to be large enough to allow detection with moderate group sizes and to preserve suitability for pharmacological reversal. GTN and CGRP produced partially overlapping behavioral profiles that were assay-, strain-, and sex-dependent. While both triggers reliably induced PMA, their effects on light aversion and grimace score diverged across strains and sexes. Together, this study provides a side-by-side evaluation of migraine-like behavioral endpoints under controlled experimental conditions, highlighting how trigger selection, strain, sex, and behavioral assay critically influence outcomes. The data support a standardized, multi-endpoint approach for preclinical migraine studies aimed at pharmacological screening while maximizing information yield and adhering to the 3Rs principle.
Humidity levels, like light and temperature, fluctuate daily yet are less predictable; however, whether humidity can entrain circadian clocks and synchronize animal behaviors with environmental variations remains unknown. Here, we investigate the circadian humidity entrainment in various insects across multiple orders. Insect species respond to humidity cycles with distinct patterns, some active during either wet/dry periods or at the arid-humid transition. When the humidity cue is removed, most species continue to show rhythmic activity associated with the previous arid-humid (AH) cycles. Fruit flies shift their activity accordingly when humidity cycles are altered and remain in the new rhythms under the following free-running conditions (FRC; constant humidity, HH). Moreover, Drosophila clock and hygrosensation mutants have lower rhythmic activity during AH and a significant reduction in rhythms after humidity entrainment (FRC with HH), indicating that core clock components and hygrosensors are essential for humidity-dependent circadian entrainment. Our findings provide strong evidence that humidity is likely to serve as a potential zeitgeber for circadian entrainment in most, but not all, insect systems and should have broad applicability and importance across animal systems. While light and temperature act as the primary zeitgebers, understanding the mechanisms of humidity entrainment will help us better interpret the behavioral patterns of terrestrial animals, particularly small insects susceptible to dehydration.
The regulation of organ size is a fundamental question in developmental biology, and insect wings provide a powerful model for elucidating the genetic mechanisms underlying morphogenesis. Although the conserved Hippo signaling pathway plays a central role in controlling tissue growth, its precise regulatory network during wing development remains incompletely understood. Here, we identify the zinc finger transcription factor OVOL as a critical mediator of Hippo signaling in insect wing development. We indicate that OVOL is essential for normal wing formation in both Locusta migratoria and Drosophila melanogaster, regulating cell proliferation and trichome patterning. Through transcriptomic analysis and functional validation, we further identify the small GTPase Rac1 as a key downstream effector of OVOL that promotes proliferative growth. Moreover, we find that OVOL expression is directly activated by the Yorkie/Scalloped (Yki/Sd) complex, the core transcriptional effector of the Hippo pathway, without forming a feedback loop. This regulation is mediated through a specific Sd-binding motif (GATAA) within the OVOL promoter. Importantly, Yki/Sd-induced Rac1 expression is dependent on OVOL. Collectively, our findings establish the Yorkie/Sd-OVOL-Rac1 pathway that governs insect wing development by promoting cell proliferation, providing mechanistic insights into organ size regulation in animals.
Small interfering RNA (siRNA) holds therapeutic promise for dermatological diseases, but clinical translation is limited by the stratum corneum barrier and the instability of naked siRNA. Nanocarrier-based systems offer effective solutions by enhancing skin penetration, improving siRNA stability, and enabling targeted intracellular delivery. This review synthesizes current evidence on nanocarrier-mediated transdermal siRNA delivery. Key design parameters: particle size, surface charge, degradability, and morphology are evaluated for their roles in skin permeation and intracellular trafficking. Stimuli-responsive nanocarriers (pH, enzymatic, light, temperature) and physical enhancement strategies, including microneedles, sonophoresis, and laser ablation, are also reviewed. Lipid-polymer hybrid nanoparticles demonstrate notable advantages in stability, biocompatibility, and co-delivery capability. Stimuli-responsive systems enable spatiotemporal control of siRNA release, while physical enhancement technologies significantly improve cutaneous permeability. Disease-specific delivery strategies tailored to pathological microenvironments including psoriasis, melanoma, and chronic wounds illustrate the feasibility of adapting material composition, structural parameters, and responsiveness to different therapeutic contexts. Advances in intelligent nanomaterials, responsive carrier engineering, and physical facilitation approaches provide a solid foundation for clinically viable transdermal siRNA therapies. Future development will benefit from integrating precise release control with disease-tailored delivery strategies to overcome biological barriers and optimize therapeutic outcomes.
Environmental endocrine disruptors (EEDs), endocrine-interfering pollutants, attract attention for potentially affecting heart diseases via epigenetics. Nonylphenol (NP), a classical representative of endocrine-disrupting chemicals, has previously been demonstrated by our research group to induce myocardial fibrosis in rats. LncRNA, a gene regulator, mediates EED-induced heart cell damage and fibrosis. This study aimed to investigate the role of long noncoding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) knockdown in NP-induced myocardial fibrosis. Small interfering RNA (siRNA) transfection was used to interfere with the expression of lncRNA OIP5-AS1 in H9C2 cells. Lactate dehydrogenase (LDH), cell Counting Kit-8 (CCK-8), transwell, quantitative real time polymerase chain reaction (qRT-PCR), and Western blot assays were employed to detect cell membrane integrity, proliferation, migration ability, and the expression of fibrosis-related genes/proteins in H9C2 cells. This process was also validated in Sprague Dawley (SD) rats. The expression of fibrosis-related factor mRNA and proteins in H9C2 cells increased, and the expression of lncRNA OIP5-AS1 was significantly upregulated after 24 h of exposure to 70 µmol/L NP. The knockdown of lncRNA OIP5-AS1 did not show differential changes in LDH activity across treatment groups. However, the knockdown of lncRNA OIP5-AS1 significantly attenuated NP-induced proliferation and migration abilities of H9C2 cells and inhibited the increase in the expression of fibrosis-related factor mRNA/proteins caused by NP. This suggested that the interference with lncRNA OIP5-AS1 expression inhibited the NP-induced myocardial fibrosis in H9C2 cells. In vivo results suggested that NP exposure and isoproterenol hydrochloride groups in rats showed accumulation of myocardial collagen fibers in the interstitial space, increased distribution and content of collagen fibers, and elevated expression of fibrosis-related proteins. The distribution range, content of collagen fibers, and expression of fibrosis-related proteins significantly reduced in rats with lncRNA OIP5-AS1 knockdown exposed to NP compared with those in the NP group. The expression of lncRNA OIP5-AS1 was upregulated in NP-treated H9C2 cells, rat hearts, and myocardial fibrosis model rats. Knockdown of lncRNA OIP5-AS1 was associated with attenuated NP-induced myocardial fibrosis and reduced collagen deposition.
Cancer immunotherapy, including immune checkpoint inhibitors (ICIs) and chimera-antigen receptor (CAR)-T cell therapy, has achieved substantial clinical success. However, response rates remain limited in many patients due to tumor-intrinsic immune evasion and immune cell dysfunction within the tumor microenvironment (TME). Rho family small GTPases are key signaling regulators of cytoskeletal dynamics, intracellular trafficking, transcription, and metabolism in cancers. Emerging evidence implicates Rho GTPase signaling in mediating immunotherapy efficiency through its context-dependent functions. Individual Rho GTPases modulate immunotherapy responses in tumor cells and various immune cells through actomyosin-mediated chemotaxis, cell junctions, cell polarity, and gene/epigenetic networks, among other pathways. The present review summarizes both the direct evidence linking Rho GTPases in tumor cells to immunotherapy responses and the indirect role of the selective Rho GTPase signaling network in various immune cells, with a focus on the recent progress in understanding the molecular mechanisms and associated outcomes of the ICIs and CAR-T cell therapies. We highlight current knowledge gaps at the intersection of Rho GTPase biology and cancer immunology and discuss therapeutic implications, proposing that selective modulation of specific Rho GTPase signaling pathways in tumor or TME immune cells represents a promising strategy to improve immunotherapy efficiency.