Search Results (2,751)

Bats are the only mammals with the ability to fly and are the second largest order after rodents, with 20 families and 1213 species (over 3000 subspecies) and are widely distributed in regions around the world except for Antarctica. What makes bats unique are their biological traits: a tolerance to zoonotic infections without getting clinical symptoms, long lifespans, a low incidence of tumors, and a high metabolism. As a result, they are receiving increasing attention in the field of life sciences, particularly in medical research. The rapid advancements in sequencing technology have made it feasible to comprehensively analyze the diverse biological characteristics of bats. This review comprehensively discusses the following: (1) The assembly and annotation overview of 77 assemblies from 54 species across 11 families and the transcriptome sequencing overview of 42 species from 7 families, focused on a comparative analysis of genomic architecture, sensory adaptations (auditory, visual, and olfactory), and immune functions. Key findings encompass marked interspecies divergence in genome size, lineage-specific expansions/contractions of immune-related gene families (APOBEC, IFN, and PYHIN), and sensory gene adaptations linked to ecological niches. Notably, echolocating bats exhibited convergent evolution in auditory genes (SLC26A5 and FOXP2), while fruit-eating bats displayed a degeneration of vision-associated genes (RHO), reflecting trade-offs between sensory specialization and ecological demands. (2) The annotation of the V (variable), D (diversity), J (joining), and C (constant) gene families in the TR and IG loci of 12 species from five families, with a focus on a comparative analysis of the differences in TR and IG genes and CDR3 repertoires between different bats and between bats and other mammals, provides us with a deeper understanding of the development and function of the immune system in organisms. Integrated genomic, transcriptomic, and immune repertoire analyses reveal that bats employ distinct antiviral strategies, primarily mediated by enhanced immune tolerance and suppressed inflammatory responses. This review provides foundational information, collaboration directions, and new perspectives for various laboratories conducting basic and applied research on the vast array of bat biology. Full article

Tendons connect animal skeletons to skeletal muscles, playing a crucial role in weight-bearing and maintaining motor functions. After decellularization, tendon extracellular matrix (tECM) retains the physicochemical characteristics similar to those of native tendons. This has made tECM a promising biomaterial in the fields of tissue engineering and regenerative medicine in recent years. This paper summarizes the origin, structure, and ECM components of animal tendons, reviews decellularization methods, and discusses recent advancements in the research and applications of decellularized tendons. Furthermore, it explores future development trends of xenogeneic decellularized tendon materials, aiming to provide a reference for fundamental research and the development of biomaterials related to decellularized tendons. Full article

Among medicinal plants, the Panax genus (family: Araliaceae) includes plant species widely recognized for their multi-faceted pharmacological attributes. The triterpenoids, designated as ginsenosides, are increasingly recognized as drug-like molecules in cancer therapies due to their therapeutic role in restricting tumor invasion, proliferation, metastasis, apoptosis, and drug resistance reversal in tumor cells. In the nanobiotechnological era, nano-delivery systems provide feasible solutions to address bottlenecks associated with traditional drug delivery methods (low bioavailability, instability in the gastrointestinal tract, high dosage requirements, side effects, poor absorption, and incomplete drug utilization in the body). The dedicated efforts for precise and effective treatment have directed the development of ginsenoside-based nano-delivery systems to achieve potent anticancer efficacies and address the limitations in ginseng pharmacokinetics, facilitating drug development trials. Studies into ginseng pharmacokinetics showed a remarkable prolonged clearance and free drug levels of ~15% (ginsenoside RB1 nanoparticles) in mice (compared to only ~5% for ginsenosides) and better antitumor efficacies, demonstrating key success in ginseng biotechnology for drug development. Delving into the nanobiotechnological interventions in ginseng-derived therapeutics, this study summarizes current advances and achievements, particularly in cancer treatment, tackles existing gaps, focuses on feasible solutions, and examines prospects of translational success. Full article

Growth differentiation factor 6 (GDF6), a member of the TGF-β superfamily, plays multifaceted roles in tumorigenesis, yet its molecular mechanisms and cancer-type-specific regulatory networks remain poorly defined. This study investigates GDF6’s context-dependent functions through pan-cancer multi-omics integration and functional validation. Transcriptomic data from TCGA (33 cancers, n = 10,535) and GTEx were analyzed to assess GDF6 dysregulation. Co-expression networks, pathway enrichment (KEGG/GO), and epigenetic interactions (m6A, m5C, m1A) were explored. Functional assays included siRNA knockdown, wound healing, and validation in immunotherapy cohorts. GDF6 exhibited bidirectional expression patterns, with downregulation in 23 cancers (e.g., GBM, BRCA) and upregulation in 7 malignancies (e.g., KIRC, PAAD). Mechanistically, GDF6 activated the PI3K-Akt/VEGF pathways, thereby promoting angiogenesis and metastasis. It modulated epigenetic regulation through interactions with m6A readers and erasers. Additionally, GDF6 reshaped the immune microenvironment by recruiting myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts. Notably, GDF6’s dual role extended to immunotherapy: it suppressed anti-PD1 efficacy but enhanced anti-PD-L1 sensitivity, linked to differential MHC-II and hypoxia-response regulation. This study deciphers GDF6’s context-dependent molecular networks, revealing its dual roles in metastasis and immune evasion. These findings highlight GDF6 as a central node in TGF-β-mediated oncogenic signaling and a potential therapeutic target for precision intervention. Full article

Caffeine is administered to preterm infants in neonatal intensive care units for prevention and treatment of apnea of prematurity. Although caffeine’s primary effect is to impact the respiratory drive of preterm infants, caffeine also has anti-inflammatory properties. This study investigated the role of caffeine on the inflammatory gene expression in THP-1 pre-monocytes exposed to lipopolysaccharide (LPS) in vitro, mimicking a clinical pro-inflammatory scenario. The effects of different physiologic dosages of caffeine administration post-LPS (treatment with caffeine) and pre-LPS (prophylaxis with caffeine) on pro-inflammatory gene expressions (TNF-α, NF-κB, IL-8, PPARγ) of the THP-1 cells were investigated. The post-LPS group showed a dose-dependent decrease in TNF-α at a caffeine concentration of 100 μM and NF-κB gene expression at 50 and 100 μM, with the implication that this is an optimal anti-inflammatory caffeine concentration range. Clinically, this would correspond to a serum caffeine level between 10 and 20 μg/mL, respectively. For the pre-LPS group, TNF-α and NF-κB gene expression decreased at all studied caffeine concentrations. These findings point to caffeine’s potential therapeutic capacity in regulating monocyte inflammatory responses to gram-negative infections in addition to regulating neuron response in the brainstem for preterm infants. Full article

At the forefront of regenerative medicine, orthobiologics represent a spectrum of biological substances that offer promising alternatives for tissue repair and regeneration. Traditional surgical treatments often involve significant risks, extended recovery periods, and may not fully restore tissue functionality, creating a strong demand for less invasive options. This paper presents a concise overview of orthobiologics, reexamining their role within the broader landscape of regenerative medicine. Beginning with a brief introduction to orthobiologics, the paper navigates through various types of biological materials and their associated mechanisms of action and clinical applications. By highlighting platelet derivatives, bone marrow-derived products, and processed adipose tissue, among others, it underscores the pivotal role of orthobiologics in prompting biological responses like cellular proliferation, differentiation, and angiogenesis, thereby fostering tissue healing. Furthermore, this paper explores the diverse applications of orthobiologics in orthopedic conditions, outlining their utility in the treatment of bone and soft-tissue injuries. Addressing clinical considerations, it discusses safety profiles, efficacy, patient selection criteria, and emerging challenges. With the limitations of traditional medicine becoming more apparent, orthobiologics offer an innovative and less invasive approach to patient care. Looking forward, this paper approaches future directions in orthobiologics research, emphasizing the need for continued innovation and exploration. Through a concise perspective, this paper aims to provide clinicians, researchers, and stakeholders with a comprehensive understanding of orthobiologics and their evolving role in regenerative medicine. Full article

Respiratory viruses such as respiratory syncytial virus (RSV) annually cause respiratory illness, which may result in substantial disease and mortality in susceptible individuals. Viruses exploit host cell machinery for replication, which engages the mitogen-activated protein kinases (MAPK) pathway. The MAPK signaling pathways are triggered by pattern recognition receptors that recognize the pathogen, infection, or external stimuli, leading to the induction and regulation of immunity and inflammation. Probenecid, used to improve renal function by inhibiting the tubular reabsorption of uric acid, has been shown to have therapeutic efficacy in reducing inflammation and blocking viral replication by inhibiting components of the MAPK pathway that preclude virus replication. This review summarizes key molecular cascades in the host response to virus recognition, infection, and replication and how this can be altered by probenecid treatment. Full article

Background: Long COVID is characterized by persistent symptoms following acute SARS-CoV-2 infection. This study aims to evaluate immune system markers, including antigen-specific antibodies, B cell subsets, and Th2-related cytokines, in individuals with long COVID and to investigate their potential impact on the development of this condition. Methods: We analyzed blood plasma from 63 individuals diagnosed with long COVID based on clinical presentation and 47 healthy individuals with COVID-19 history but no clinical symptoms. Antigen-specific IgG antibodies were measured using commercial ELISA kits. Lymphocyte subpopulations were assessed via flow cytometry and a gating strategy based on CD27 and CD38. Th2 cytokines (IL-4, IL-5, IL-13) were quantified using the xMAP multiplex assay. Results: We noted no significant differences in IgG levels between groups. Notably, individuals with long COVID demonstrated a higher percentage of naive mature B cells (CD27−CD38+), while transitional (CD27−CD38+++) and double-negative (DN, CD27−CD38-) cells were significantly reduced. Elevated levels of IL-5 and IL-13 were observed in long COVID patients. Classification analysis revealed that the percentage of transitional B cells (CD27−CD38+++) was a strong predictor of long COVID. Conclusions: Our findings highlight alterations in B cell dynamics among individuals with long COVID, which may contribute to autoimmune processes. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by complex pathogenesis involving dysregulated immunity and gut microbiota imbalance, demanding innovative therapeutic strategies. This study investigates the synergistic therapeutic potential of pomegranate peel–hawthorn combinations and their active constituents (ellagic acid and maslinic acid) through an integrative approach combining network pharmacology, in vitro/in vivo experiments, and gut microbiota analysis. Network pharmacology identified 61 shared therapeutic targets (p < 0.05 for pathway enrichment) and revealed complementary mechanisms: pomegranate peel primarily modulated AGE-RAGE/PI3K-Akt pathways, while hawthorn targeted IL-17/NF-κB signaling. Experimental validation demonstrated potent synergistic anti-inflammatory effects (combination index < 1), with optimal combinations reducing nitric oxide production by 52.35% (herbal extracts, p < 0.05) and 74.4% (active monomers, p < 0.05). In DSS-induced UC mice, combinatorial therapies significantly suppressed pro-inflammatory cytokines (TNF-α: 204.78 vs. 446.52 pg/mL in UC group, p < 0.05; IL-6: 33.19 vs. 64.86 pg/mL, p < 0.05), restored colonic SOD activity (72.31 vs. 50.10 U/mg·prot in UC group, p < 0.01), and alleviated histopathological damage, outperforming monotherapeutics. Gut microbiota analysis revealed the recovery of α-diversity indices and normalized Bacteroidota/Bacillota ratios. Mechanistically, the combinations suppressed MAPK/NF-κB signaling cascades, reducing p-p38/p38 (p < 0.01 vs. UC group) and p-ERK1/2/ERK1/2 (p < 0.01 vs. UC group) phosphorylation. These findings establish that pomegranate peel–hawthorn formulations exert multi-modal therapeutic effects through the synergistic inhibition of pathways, mitigation of oxidative stress, and restoration of the microbiota, offering a scientifically validated approach for UC management rooted in traditional medicine principles. Full article

Multiple myeloma (MM) is one of the most frequent hematological malignancies. Most MM cases relapse, which is associated with poor prognosis. MM-related tumor suppressor genes are not totally known yet. SOX7 is one of the tumor suppressor candidates located in 8p23.1, a recurrently deleted region in MM. Here, we evaluated the genetic and epigenetic aberrancies of SOX7 in diagnostic or relapsed MM as well as smoldering MM (SMM) and plasma cell leukemia (PCL). Publicly available datasets were reanalyzed to evaluate SOX7 copy number, promoter methylation, transcript levels in MM or related neoplasms and to evaluate mutation rates in MM cases. qPCR and qRT-PCR with an in-house MM cohort were performed to cross-validate SOX7 copy number and transcript level estimates. SOX7 deletions were frequent in newly diagnosed and relapsed MM cases. SOX7 promoter hypermethylation was observed in MM cell lines, MM cases, and PCL cases. Importantly, SOX7 was transcriptionally silent in MM cell lines and underexpressed in MM and high-risk SMM cases. Integrative analyses of patient-matched diagnostic and relapsed MM tumor tissues revealed moderate positive correlations between SOX7 copy numbers. SOX7 deletion and promoter methylation levels had a tendency to be mutually exclusive. SOX7 promoter methylation levels were significantly higher in relapsed cases compared to the diagnostic ones. SOX7 mutations were rare in MM cases. SOX7 underexpression may be due to genetic and/or epigenetic alterations in newly diagnosed and relapsed MM. These genetic and epigenetic aberrations can serve as diagnostic or prognostic biomarkers for MM and allied neoplasms. Future research will reveal whether SOX7 inactivation has a role in development of these plasma cell neoplasms. Full article

China, the largest global producer of sweet potatoes, faces significant threats from viral diseases, particularly in Fujian Province, where sweet potatoes are the second most important food crop after rice. This study identified 11 viruses, including sweet potato feathery mottle virus (SPFMV) and sweet potato chlorotic stunt virus (SPCSV), infecting sweet potatoes in Fujian. Sequence comparisons revealed diverse strains from various sources. Virus prevalence varied across regions, with Quanzhou, Fuzhou, and Putian severely affected, detecting 10, 9, and 7 viruses, respectively, compared to only 3 in Sanming and Longyan. In particular, sweet potato virus disease (SPVD) caused the most severe damage during the seeding stages, resulting in dwarfing and leaf deformation, while the damage was lighter during the growth period, manifesting as the yellowing and brittleness of the leaves, ultimately reducing the yield. Compound infestations predominated, with between 0 and 6 viruses infecting different sweet potato varieties. Single-virus infections were observed for sweet potato virus 2 (SPV2), sweet potato symptomless virus 1 (SPSMV-1), and sweet potato pakakuy virus (SPPV), while others, particularly SPCSV, were frequently co-infected with SPFMV, leading to SPVD development. Further analysis showed that the RNase3 expression of SPCSV was correlated with the SPVD severity in sweet potato. These findings provide insights into the epidemiology of sweet potato viruses and serve as a reference for developing targeted disease management strategies. Full article

Migraine is a chronic neurovascular disease with unclear pathophysiological mechanisms. In this study, its pathogenic mechanisms were investigated through bioinformatics analysis of migraine-related pathways and key genes. Female Sprague Dawley rats were divided into control and migraine model groups. The control group received saline, while the migraine model group received nitroglycerin (NTG) to induce migraines over four weeks. Migraine-like behaviors were assessed within two hours following the final NTG injection. Genes of hypothalamus were identified using DESeq2. Gene ontology enrichment and KEGG pathway analyses were conducted, followed by the identification of hub genes based on protein interaction networks by using algorithms such as Closeness, Degree, and Maximum Neighborhood Component. Rats with NTG-induced migraine showed increased head scratching and cage climbing and a reduced sucrose preference. Transcriptome analysis revealed 1564 differentially expressed genes, with 1233 upregulated and 331 downregulated. Pathways linked to inflammation, PI3K–Akt signaling, and cytokine–cytokine receptor interactions were found to have enriched expression of several genes. Further protein interaction network analysis identified nine hub genes: Alb, Tgfb1, Cd4, Ptprc, Itgb1, Icam1, Col1a1, Pxdn, and Itgad. These findings suggest that migraine involves PI3K–Akt signaling and cytokine–cytokine receptor interactions, providing insights into molecular mechanisms and potential therapeutic targets. However, the study was limited by a small sample size and reliance on a single experimental model, which may constrain the clinical applicability of the findings. Full article

The detection of circulating tumor cells (CTCs) using immunoaffinity-based methods often relies on epithelial-related markers, which may bias the selection of CTCs and limit the biological information obtained, depending on the targeted antigens. Herein, we compared the molecular profiles and clinical significance of CTCs based on the expression of epithelial-related markers (EPCAM, EGFR, and MET) in patients with head and neck squamous-cell carcinoma (HNSCC). CTCs were detected using density gradient separation and CD45-negative selection, followed by quantitative PCR for epithelial-related marker expression. Expression profiles of epithelial–mesenchymal transition (EMT)-related (VIM, CDH1, CDH2, SNAI1, ZEB1, ZEB2, and TWIST1) and immune-regulatory (CD274 and PDCD1LG2) genes were compared. Moreover, the association between marker expression and clinical factors was analyzed. Among the 60 patients with CTCs, 48 (80.0%), 20 (33.3%), and 31 (51.7%) were positive for EPCAM, EGFR, and MET, respectively. A significant correlation was observed between CTCs expressing EPCAM and EGFR. CTCs expressing distinct markers showed differing EMT-related and immune-regulatory gene expression. EPCAM+ CTCs were associated with advanced-stage disease, while EGFR+ CTCs were correlated with locoregional relapse and shorter progression-free survival (p = 0.007; hazard ratio = 3.254). Patients with EPCAM/EGFR double-positive CTCs had the poorest prognosis. These findings emphasize the importance of marker selection in liquid biopsy technologies and highlight the need for improved detection methods and the further investigation of CTC biology. Full article

Injectable Platelet-Rich Fibrin (i-PRF) has emerged as a promising tool in regenerative medicine, particularly in orthopedics, due to its unique biological properties and ease of preparation. i-PRF is an autologous platelet concentrate derived through a simple, anticoagulant-free centrifugation process, resulting in a liquid matrix enriched with fibrin, leukocytes, and growth factors. These components promote tissue regeneration, angiogenesis, and anti-inflammatory responses, making i-PRF suitable for bone and cartilage repair as well as drug delivery systems. This review discusses the history, biological mechanisms, and clinical applications of i-PRF in orthopedics, highlighting its potential advantages over traditional platelet-rich plasma (PRP). Furthermore, we address the challenges and limitations of i-PRF, including drug stability, release control, and bioactive interactions, underscoring the need for further research to optimize its therapeutic efficacy. Full article

The bla_OXA-1 gene encodes an oxacillin-hydrolyzing beta-lactamase of extended-spectrum beta-lactamase (ESBL)-producing microorganisms. The bla_OXA-1 gene is found in the resistomes of some Enterobacteriaceae, Morganellaceae, Pasteurellaceae, Moraxellaceae, Aeromonadaceae, Pseudomonadaceae, Yersiniaceae, and Vibrionaceae. Most ESBL detection methods, including those to detect OXA-1-producing microorganisms, are time-consuming, and require specialized equipment and qualified personnel. Here, we report a new CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)/Cas12a-based detection assay coupled with polymerase chain reaction (PCR) to sensitively detect OXA-1-bearing microorganisms. The PCR-coupled CRISPR/Cas12a-based fluorescence assay includes (i) a pre-amplification step and (ii) a nucleic acid detection step. The pre-amplification step is based on a commonly used PCR, and the detection step is based on the CRISPR/Cas12a property to nonspecifically hydrolyze single-stranded DNA fluorescent reporter molecules. The pre-amplification step takes 65 min, and the detection step is shortened and takes only 5 min. The developed assay can easily detect single (1.25) copies of the bla_OXA-1 gene in a reaction and is efficient not only in the detection of a bla_OXA-1 model matrix but also in the detection of bla_OXA-1-positive microorganisms. We hope that our assay has the potential to improve the monitoring of OXA-1-producing microorganisms and therefore contribute to mitigating the deadly global threat of antibiotic-resistant microorganisms. Full article