Search Results (316)

Background/Objectives: We evaluated Goreisan, a traditional Chinese medicine, for its effects on nephrotic syndrome in a rat model. Methods: Male Sprague–Dawley rats underwent right nephrectomy at 5 weeks of age, followed by adriamycin administration (5 mg/kg) at 6 and 8 weeks of age to induce nephrotic syndrome. At 10 weeks, rats were divided into three groups: vehicle (control), Goreisan 0.5 g/kg (GL), and Goreisan 1.0 g/kg (GH). Goreisan was administered daily for 4 weeks. At 14 weeks, blood, urine, mRNA expressions, and kidney histopathology were analyzed. Data were analyzed using one-way ANOVA followed by Tukey–Kramer post hoc testing. Results: Goreisan prevented worsening kidney function, with reduced glomerular and tubulointerstitial damage, lower systemic and intrarenal 8-hydroxy-2′-deoxyguanosine levels, and lower plasma aldosterone levels and expression of intrarenal renin–angiotensin–aldosterone system (RAAS)-related factors. Urine volume significantly increased in GL and GH groups compared with the control group. In the GH group, urine volume increased markedly (Δ urine volume: 10.0 ± 2.6 mL/day), whereas it tended to decrease in the Vehicle group (Δ urine volume: −1.3 ± 2.5 mL/day). Urine osmolality was lower in the GH group, with a larger decrease in Δ urine osmolality (−616.3 ± 132.8 mOsm/L). These changes occurred without an increase in urinary sodium excretion, suggesting an aquaretic effect independent of natriuresis. Creatinine clearance (CCr/kg) declined markedly in the Vehicle group but was significantly preserved in the GH group (Δ CCr/kg: −2.2 ± 0.19 vs. −0.7 ± 0.28), indicating renoprotective effects. No differences were found in serum arginine–vasopressin levels. Real-time PCR and immunohistochemical staining showed no significant differences in aquaporin (AQP) mRNA expression (AQP1, AQP2, AQP3, and AQP4), but AQP2 localization to the apical membrane in the collecting ducts was reduced with Goreisan treatment. Conclusions: Goreisan demonstrates kidney-protective and diuretic effects in nephrotic syndrome, potentially through reducing systemic oxidative stress, modulating RAAS activation, and altering AQP2 trafficking. Full article

The genus Tortula is one of the most diverse and morphologically complex groups within Pottiaceae. This study presents both morphological and phylogenetic evidence for the recognition of a new species, T. murciana, within the T. subulata complex. The new species is distinguished by a unique combination of traits, including a translucent leaf lamina, upper laminal cells with 3–7 simple, wart-like papillae (verrucae), and middle laminal cells 16–24(35) µm wide, that are much higher near the costa than at the leaf margins. The ventral epidermal cells of the costa at mid-leaf are quadrate to spherical and inflated. The costa is robust, up to 140 µm wide at mid-leaf and papillose on the dorsal side. The apical cell of the apiculus is typically hyaline and often deciduous. The leaf border is usually absent or poorly developed. The basal membrane of the peristome is 0.70–0.90 mm long, with a reticulate pattern where the lumina are delimited by strongly developed muri ornamented with globose clusters of ear-like lobes (auricles). Phylogenetic analysis of the nuclear ITS region places T. murciana within the T. subulata complex, clearly distinguishing it from T. mucronifolia and T. subulata var. graeffii, with which it shares the closest morphological similarity. Although most specimens can be identified morphologically, some remain difficult to name, making them a semi-cryptic species. The new species is formally diagnosed, described, illustrated, and compared to similar taxa. A key to all species in the complex is also provided. Full article

Pollen tube growth entails complex molecular interactions between the cytoskeletal apparatus and membrane trafficking. Tip growth involves polarized distribution of proteins and lipids along the plasma membrane, including liquid-ordered microdomains, rich in sterols and sphingolipids (lipid rafts), in the apical/subapical region of tobacco pollen tubes. Intriguingly, biochemical characterization of detergent-insoluble membranes purified from tobacco pollen tubes revealed the presence of both actin and tubulin. Here, we report that inhibition of sterol biosynthesis altered lipid rafts and lowered the association of tubulin with detergent-insoluble membranes. Our results showed that sterol depletion increased the number of microtubules in the subapical region, altered microtubule distribution and affected microtubule bundling activity. Oryzalin washout experiments also suggested that lipid-ordered domains could play a role in regulating microtubule nucleation/regrowth. Full article

The cell surface proteome of polarized epithelial cells plays a central role in barrier function, signaling, and vectorial transport, yet the quantitative characterization of their surface proteins remains technically challenging. We developed an optimized chemoproteomic strategy specifically tailored to studying the surface proteins of polarized cells while keeping membrane integrity intact. By applying a disulfide-linked membrane-impermeable biotin reagent, labeling was restricted to extracellular regions of transmembrane proteins (TMPs) and secreted proteins, thereby minimizing contributions from intracellular contaminants. Following biotinylated peptide-level or protein-level enrichment and mass spectrometric analysis, we systematically compared data-dependent (DDA) and data-independent acquisition (DIA) approaches, showing that while DIA increases proteome coverage, DDA more reliably identifies biotinylated peptides in our studies. To ensure robustness, we established replicate-based normalization and contaminant-aware quality control metrics that minimize biases from proteins in cell culture medium and damaged cells. The application of the workflow to Madin–Darby canine kidney (MDCK) II epithelial monolayers enabled the large-scale quantification of apical versus basolateral domains, yielding over 2100 proteins, with 235 showing significant polarized distribution, in agreement with known biology. This method offers high specificity for the extracellular labeling and quantitative resolution of cell surface protein (CSP) polarization, providing a powerful platform for studying epithelial biology and identifying extracellular epitopes relevant to diagnostics and therapeutic targeting. Full article

The thymus and parathyroid glands share a common embryological origin from the third pharyngeal pouch, yet their potential morphological and functional interconnections remain insufficiently explored. We conducted a comparative study integrating immunohistochemistry (IHC) and SEM on human thymic tissue, parathyroid adenomas, and parathyroid tissue excised during thyroidectomy. IHC staining targeted Thymosin-α1, CaSR, and PTH1R, with semi-quantitative evaluation of staining intensity and distribution. SEM analysis was performed at multiple magnifications to assess stromal organization and microvascular relief. Non-parametric statistical tests (Kruskal–Wallis with Mann–Whitney post hoc comparisons) were applied to clinical and laboratory data across the three cohorts. Scanning electron microscopy (SEM) revealed convergent ultrastructural features between thymus and parathyroid, including reticular stromal meshes and vascular grooves suggestive of comparable microcirculatory organization. IHC demonstrated robust Thymosin expression in thymus, with heterogeneous/apical distribution in parathyroid tissue; CaSR showed strong membranous and cytoplasmic expression in parathyroid, but weak diffuse signal in thymus; PTH1R exhibited low-to-moderate expression in thymus and moderate heterogeneous expression in parathyroid, with apical accentuation in adenomas. Statistical analysis confirmed significant differences in ionized calcium, PTH, and anti-AChR titers among the three cohorts (all p < 0.001), while TSH and calcitonin did not differ significantly. Our findings strengthen the hypothesis of a morpho-functional parathyroid–thymus axis. The robust parathyroid expression of CaSR and PTH1R aligns with established roles in calcium–PTH homeostasis, while the novel detection of Thymosin in parathyroid tissue suggests an expanded functional repertoire. These results highlight a continuum between embryological proximity and adult tissue cross-talk, with potential clinical implications for parathyroid pathology and immune regulation. Full article

Entomopathogenic viruses offer an eco-friendly biological approach for pest control, but their relatively slow action often limits practical applications. Synergistic interactions between insect viruses and chemical pesticides can amplify their control efficacy, reduce insecticide use, and thus alleviate associated risks. Here, we evaluated the combined effects of the gomphocerinae permutotetra-like virus (GPV) and the neurotoxic insecticide imidacloprid against nymphs of Locusta migratoria. In toxicity tests, neither GPV nor imidacloprid alone caused mortality from acute toxicity after 12 h (<30%), but co-application led to marked acute synergistic toxicity, significantly increasing mortality to 87% within 12 h and 93% by 96 h. Importantly, histopathological examination revealed that the synergistic treatment caused severe midgut damage, such as disrupted or absent microvilli, extensive cellular debris in the gut lumen, cell detachment from the basal lamina, and apical displacement of nuclei. Furthermore, RNA-seq and biochemical analyses showed that the cotreatment aberrantly regulated key genes involved in peritrophic membrane integrity, substantially elevated immune responses, and disrupted energy homeostasis, which collectively led to death. These critical insights on the mechanisms underpinning the synergistic action of viral and traditional chemical agents underscore the potential of such integrated strategies to rapidly, effectively, and safely control pests. Full article

Microfluidics enables precise manipulation of scarce Traditional Chinese Medicine (TCM) samples while accelerating analysis and enhancing sensitivity. Device-level structures explain these gains: staggered herringbone and serpentine mixers overcome low-Reynolds-number constraints to shorten diffusion distances and reduce incubation time; flow-focusing or T-junction droplet generators create one-droplet–one-reaction compartments that suppress cross-talk and support high-throughput screening; “Christmas-tree” gradient generators deliver quantitative dosing landscapes for mechanism-aware assays; micropillar/weir arrays and nanostructured capture surfaces raise surface-to-volume ratios and probe density, improving capture efficiency and limits of detection; porous-membrane, perfused organ-on-a-chip architectures recreate apical–basolateral transport and physiological shear, enabling metabolism-aware pharmacology and predictive toxicology; wax-patterned paper microfluidics (µPADs) use capillary networks for instrument-free metering in field settings; and lab-on-a-disc radial channels/valves exploit centrifugal pumping for parallelised workflows. Framed by key performance indicators—sensitivity (LOD/LOQ), reliability/reproducibility, time-to-result, throughput, sample volume, and sustainability/cost—this review synthesises how such structures translate into value across TCM quality/safety control, toxicology, pharmacology, screening, and delivery. Emphasis on structure–function relationships clarifies where microfluidics most effectively closes gaps between chemical fingerprints and biological potency and indicates practical routes for standardisation and deployment. Full article

Introduction: Although the incidence of mechanical complications of myocardial infarction is decreasing, the associated mortality rate remains high. Such complications require an early diagnosis and multidisciplinary management. In most cases, surgery is the only definitive treatment, despite it being associated with high peri-operative mortality and morbidity. An intra-aortic balloon pump (IABP) or Extracorporeal Membrane Oxygenation (ECMO) may also be required for unstable patients. After the employment of mechanical assistance, ultrasound and chemical parameters are associated with successful weaning, indicating adequate cardiac function, perfusion, and oxygen delivery. Case presentation: The aim of this case report is to describe the weaning from the extracorporeal support in a case of post-myocardial-infarction ventricular septal defect (VSD) and Left ventricle (LV) apical aneurysm. The patient underwent surgery for VSD closure and aneurysm exclusion. After the emergency surgery, the patient developed a severe post-cardiotomy cardiogenic shock, which required veno-arterial femoral–femoral extracorporeal membrane oxygenation (VA-ff-ECMO), IABP, and maximal pharmacologic support. During the ICU stay, we weaned the patient from the ECMO support based on transesophageal echocardiography (TEE) imaging and pulmonary artery catheter (PAC) monitoring and quantified the shunt fraction. On the fifth post-operative day, we started the weaning trial. Hemodynamic and ultrasound monitoring showed an adequate cardiac function, and the shunt fraction calculated with both the ultrasound parameters and Fick’s law was acceptable. We removed the ECMO the day after, and the weaning was successful. Discussion: Data deriving from the Swan–Ganz catheter has been found to be important in guiding the process of weaning a patient from extracorporeal support. Nevertheless, the TEE played a pivotal role in the decision-making process and in clinical management. We reduced the ECMO blood flow following a real-time echocardiographic cardiac function assessment. Conclusions: Following the fundamental guides for both PAC monitoring and TEE imaging, we successfully removed the extracorporeal support, with a positive outcome. Full article

The cell wall integrity pathway is activated in response to cell wall stress (CWS). The defense system in aspergilli employs three transcription factors—RlmA, MsnA, and CrzA—which also facilitate adaptation to various abiotic stressors and involve alterations in cytosolic osmolyte composition and membrane lipid profiles. However, their role in adaptation to CWS remains unclear. In Aspergillus niger, CWS induced by Congo red and calcofluor white caused a pronounced cessation of apical growth, accompanied by hyphal globular swelling and an increase in chitin and glucan content in the cell wall. Regarding the osmolyte composition, which predominantly consists of low levels of glycerol and mannitol, glycerol levels were reduced under CWS. Neither the composition nor the amounts of membrane and storage lipids changed following CWS; however, the degree of unsaturation of phospholipids increased due to a higher proportion of linolenic acid, potentially enhancing membrane fluidity. These minor rearrangements of membrane lipids and osmolytes do not confirm their involvement in the adaptation to CWS induced by Congo red and calcofluor white, contrary to previous assumptions based on studies of cell wall integrity pathways. Full article

Background/Objectives: Sepsis-induced cholestasis is caused by the release of inflammatory cytokines from lipopolysaccharide (LPS), a component of Gram-negative bacteria. No established therapy exists for this condition. We ascertained the anticholestatic potential of obeticholic acid (OCA), a potent FXR agonist, in a rat model of LPS-induced cholestasis. Methods: Male Wistar rats were randomized into Control, OCA (20 mg/kg/day, i.p., 6 days), LPS (total dose of 6.5 mg/kg, i.p., in the last 2 days, respectively), and OCA + LPS groups. Then, we assessed the serum cholestasis marker, alkaline phosphatase (ALP), and taurocholate-stimulated bile salt output. mRNA/protein levels of the main apical and sinusoidal uptake and efflux carriers were assessed by either or both RT-qPCR and Western blot. Bsep and Mrp2 localization was assessed by immunohistochemistry followed by confocal microscopy and image analysis. Inflammatory cytokines were measured in serum by ELISA. Results: OCA significantly attenuates inflammatory cytokine release and normalizes serum ALP in LPS-treated rats. OCA also increased the biliary output of the Bsep substrate, taurocholate, and partially improved total Bsep at both mRNA and protein levels. Furthermore, OCA fully normalizes Bsep in the canalicular plasma membrane fraction, suggesting improved membrane localization, a finding further confirmed by confocal microscopy. OCA sustained the beneficial downregulation of uptake transporters Ntcp and Oatp2 or the upregulation of the efflux pump Mrp3, both of which serve to minimize hepatocellular bile-salt accumulation. Conclusions: OCA prevents bile-salt accumulation in LPS-induced cholestasis by enhancing Bsep expression and localization, and by mitigating inflammation. This makes OCA a promising therapeutic candidate for sepsis-induced cholestasis. Full article

Background: Periodontally accelerated osteogenic orthodontics (PAOO) is a surgical procedure to accelerate orthodontic tooth movement and minimize periodontal complications. This study surveyed U.S. periodontists to assess various aspects of the procedure as regards prevalence, training, and execution. Methods: The authors developed a unique questionnaire, the first national study of this type, housed on the Qualtrics^® survey platform, to analyze trends in PAOO training and use. Unique recruitment emails were sent to 3154 members of the American Academy of Periodontology. 449 U.S. periodontists/3154 surveyed (14.2%) responded to this web-based, anonymized survey. IBM statistical software (SPSS V28) was used for data analysis. Results: Among respondents, PAOO training was received during residency (32.7%) and by continuing education (CE) (50.8%), with higher CE (57.3%) by those who did not receive PAOO residency training (p < 0.001). 38.5% of periodontists perform PAOO, and those most likely to perform PAOO had both PAOO residency training and CE, with 78.5% performing 1–5 cases/year. Most (87.7%) received 1–2 PAOO referrals/year from orthodontists or general dentists. Differences in techniques and materials were the type of bone graft or membrane used, the position of corticotomies, and the timing of orthodontic movement. The primary PAOO goal was “rapid tooth movement” (41.1%) and to “increase the alveolar housing” (37.2%). The secondary (38%) and tertiary (37.2%) ranked goals were “augment dehiscence or fenestration”, with the “prevention of apical root resorption” ranked as their quaternary goal. Conclusions: The results of this survey provide data on the trends, training, and use of PAOO among U.S. periodontists. This information may aid in developing residency curriculum and performing PAOO research. Full article

Sulfur metabolism plays an important role in plant growth and environmental adaptation. Sulfate transporters (SULTRs) are essential players that mediate sulfur acquisition and distribution in many plants, thereby influencing the cellular redox homeostasis under abiotic stress. In this study, we identified 16 putative HvSULTRs genes in barley at the genome-wide level. The conservation and divergence of the SULTR gene family were assessed through a phylogenetic tree and gene structure analysis, revealing that these genes are closely distributed along the chromosomes. Furthermore, the expression pattern of SULTRs in multiple tissues, including flower, root, leaf, stem, seeds, female, male, root meristem, and apical meristem, were analyzed among ten land plants using a public database. Interestingly, the expression of HvSULTR2, HvSULTR4, and HvSULTR5 was upregulated after four days of heat treatment, suggesting their importance in barley’s adaptive response to heat stress. In addition, HvSULTR11 was confirmed to be localized at the plasma membrane and display functional interactions with Hv14-3-3A/Hv14-3-3D. In addition, haplotypes of the HvSULTR11 based on SNP (Single Nucleotide Polymorphism) were divided into ten types across 123 barley varieties. Together, these results provide a new clue to clarify the molecular mechanism of SULTRs in stress response and a new candidate gene resource to enhance the stress (e.g., heat and drought) tolerance in barley. Full article

Total internal reflection fluorescence (TIRF) microscopy excites fluorophores within a few hundred nanometers of the sample–substrate interface, enabling high-contrast imaging near the cell membrane. When cultured cells differentiate, the membrane in contact with the coverslip generally acquires basal characteristics, while the opposite membrane develops apical features. Consequently, conventional TIRF microscopy is limited to imaging the basal surface. We developed an immersed-prism TIRF (IP-TIRF) microscope, in which a prism immersed in the culture medium generates TIR at the cell/medium–prism interface, illuminating the apical membrane and reducing cytosolic background. In proof-of-principle experiments, we imaged fluorescent beads and 3xmNeonGreen-tagged intraflagellar transport (IFT) particles in cilia, and compared the performance with confocal microscopy. In cellular regions where both methods can be applied (such as the IFT base pool), on average, IP-TIRF achieved approximately 1.8 times the contrast-to-noise ratio (CNR~31) compared to confocal microscopy. Furthermore, IFT-particle motion was detected in IP-TIRF image sequences and Kymographs of cilia, with adequate spatial resolution. Kymograph analysis revealed an average anterograde IFT velocity of 0.156 ± 0.071 µm/s and an average retrograde velocity of 0.020 ± 0.007 µm/s, approximately one-quarter and one-twentieth, respectively, of the values reported for mammalian primary cilia, which we attribute to acquisition at room temperature rather than physiological conditions. Therefore, these velocity measurements should be regarded as proof-of-principle demonstrations obtained at room temperature, not as validated physiological transport rates. Our IP-TIRF method provides a high-resolution, cost-effective, and broadly accessible approach for imaging the apical membrane in live cells. Full article

Odontogenic sinusitis is a highly prevalent yet frequently overlooked condition. Since anatomically, the roots of the upper molars and premolars may be in proximity to the maxillary sinus, apical periodontitis affecting these teeth may lead to the development of sinus membrane thickening suggestive of odontogenic sinusitis. The present cross-sectional study aimed to investigate the relationship between images suggestive of apical periodontitis and alterations in the maxillary sinus. One hundred and thirty Cone Beam Computed Tomographies (CBCTs) of the posterior maxilla were examined for the presence of apical radiolucent lesions and thickening of the sinus membrane. The relationship between the distance of the lesions from the sinus and the prevalence of sinus alterations was described and compared using a chi-squared test and logistic regression models. In the sample studied, 16.12% and 45.96% of the sinus images suggested mucositis and sinusitis, respectively. The mere presence of radiolucent apical lesions was not related to sinus alterations. However, lesions breaking through the cortical floor of the sinus were associated with a larger mucosal thickness, reaching statistical significance on the left side. Estimation of the magnitude showed that increasing the sample size would lead to a statistical difference on the right side as well. Thus, it can be concluded that, in cases where lesions suggesting apical periodontitis are closely related to the sinus floor, breaking though the cortical bone of the maxillary sinus floor, the prevalence of sinus mucosal thickening, indicating mucositis or sinusitis, is greater. Full article

Background: Toxoplasma gondii (T. gondii) infection causes serious diseases in immunocompromised patients and causes congenital toxoplasmosis in infants. T. gondii microneme protein 8 (MIC8) and apical membrane antigen 1 (AMA1) are essential proteins involved in parasitic invasion. Methods: In this study, we generated virus-like particles (VLPs) and recombinant vaccinia virus (rVV) containing MIC8 or AMA1 proteins. Vaccine efficacy was evaluated in mice (BALB/c) upon challenge infection with T. gondii ME49. Results: Intramuscular immunization with heterologous vaccines (rVV + VLPs; rVV for prime and VLPs for boost) elicited T. gondii-specific IgG antibody responses in mice. Four weeks after the boost, all mice were orally challenged with T. gondii ME49, and protective immunity was assessed. The responses of antibody-secreting cells for IgG2a and IgG2b and those of memory B cells and CD4+ and CD8+ T cells were higher in the rVV + VLP group than in the VLP + VLP group. The rVV + VLP group exhibited a significant reduction in cyst count in the brain. Conclusions: These findings indicate that heterologous vaccination with vaccinia viruses and VLPs improves vaccine efficacy. Full article