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Experimental Cell Research Jun 2024The extracellular matrix surrounding the tumor undergoes changes in its organization during the metastasis process. The present study aims to quantify total collagen,...
The extracellular matrix surrounding the tumor undergoes changes in its organization during the metastasis process. The present study aims to quantify total collagen, collagen I (Col I) and collagen III (Col III), analyze the alignment of collagen fibers and assess the basement membrane integrity in samples from patients with metastatic and non-metastatic prostate cancer. Tissue samples from 60 patients were classified into groups based on prognostic parameters: better prognosis (n = 20), worse prognosis without metastasis (n = 23) and metastatic (n = 17). Picrosirius red with further analysis under polarizing microscope was used to quantify (with validation using immunohistochemistry) and analyze collagen alignment, and Periodic Acid Schiff staining was used to analyze the basement membrane integrity. The Col I/Col III ratio was found to be higher in the metastatic group than in the groups with better prognosis (p = 0.012) and worse prognosis without metastasis (p = 0.018). Basement membrane integrity constitution in malignant tumor tissue differed from that of adjacent non-tumor tissue (p < 0.001). Moreover, the worsening in the tumor tissue integrity was positively correlated with worse prognostic parameters. All in all, absence of Col III and basement membrane integrity might be indicators of poor prognosis in prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Basement Membrane; Prognosis; Biomarkers, Tumor; Aged; Collagen Type III; Middle Aged; Collagen Type I; Extracellular Matrix
PubMed: 38735620
DOI: 10.1016/j.yexcr.2024.114077 -
Anatomia, Histologia, Embryologia May 2024Identifying and analysing distinct blood cells is crucial for the diagnosis and treatment of diseases in the field of biomedicine. The present study was undertaken to...
Identifying and analysing distinct blood cells is crucial for the diagnosis and treatment of diseases in the field of biomedicine. The present study was undertaken to study the cytomorphological and cytochemical characteristics of the blood cells of Zoar, a non-descript indigenous breed of chicken extensively reared under backyard poultry farming in Mizoram, India. For this study, 2 mL of blood samples were aseptically collected from the wings veins of 12 chickens and were processed for light microscopic study under standard protocols. The matured erythrocytes were elliptical, while the immature erythrocytes appeared oval. The heterophils were positive for SBB (SBB), Periodic Acid Schiff (PAS), acid phosphatase, alkaline phosphatase and Arylsulphatase while the eosinophils were positive for SBB, PAS, alkaline phosphatase, cytochrome oxidase and peroxidase. The basophils of were positive for toluidine blue while the thrombocytes were positive for PAS. These cytochemical and cytoenzymatic staining properties plays a very important role in diagnosis, differentiation, and classification of leukaemias.
Topics: Animals; Chickens; India; Erythrocytes; Eosinophils; Blood Cells; Blood Platelets; Alkaline Phosphatase; Basophils; Acid Phosphatase; Electron Transport Complex IV
PubMed: 38735037
DOI: 10.1111/ahe.13054 -
International Journal of Molecular... Apr 2024Kidney ischemia and reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI), characterized by tubular injury and kidney dysfunction. Salvador...
Kidney ischemia and reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI), characterized by tubular injury and kidney dysfunction. Salvador family WW domain containing protein 1 (SAV1) is a key component of the Hippo pathway and plays a crucial role in the regulation of organ size and tissue regeneration. However, whether SAV1 plays a role in kidney IRI is not investigated. In this study, we investigated the role of SAV1 in kidney injury and regeneration following IRI. A proximal tubule-specific knockout of in kidneys () was generated, and wild-type and mice underwent kidney IRI or sham operation. Plasma creatinine and blood urea nitrogen were measured to assess kidney function. Histological studies, including periodic acid-Schiff staining and immunohistochemistry, were conducted to assess tubular injury, SAV1 expression, and cell proliferation. Western blot analysis was employed to assess the Hippo pathway-related and proliferation-related proteins. SAV1 exhibited faint expression in the proximal tubules and was predominantly expressed in the connecting tubule to the collecting duct. At 48 h after IRI, mice continued to exhibit severe kidney dysfunction, compared to attenuated kidney dysfunction in wild-type mice. Consistent with the functional data, severe tubular damage induced by kidney IRI in the cortex was significantly decreased in wild-type mice at 48 h after IRI but not in mice. Furthermore, 48 h after IRI, the number of Ki67-positive cells in the cortex was significantly higher in wild-type mice than mice. After IRI, activation and expression of Hippo pathway-related proteins were enhanced, with no significant differences observed between wild-type and mice. Notably, at 48 h after IRI, protein kinase B activation (AKT) was significantly enhanced in mice compared to wild-type mice. This study demonstrates that deficiency in the kidney proximal tubule worsens the injury and delays kidney regeneration after IRI, potentially through the overactivation of AKT.
Topics: Animals; Male; Mice; Acute Kidney Injury; Cell Cycle Proteins; Cell Proliferation; Disease Models, Animal; Hippo Signaling Pathway; Kidney Tubules, Proximal; Mice, Inbred C57BL; Mice, Knockout; Reperfusion Injury; Signal Transduction
PubMed: 38731829
DOI: 10.3390/ijms25094610 -
Journal of Ethnopharmacology Sep 2024Coptidis rhizoma, first recorded in the "Shen Nong's Herbal Classic", is one of the traditional Chinese medicine (TCM) used to treat infectious diseases, with reputed...
ETHNOPHARMACOLOGICAL RELEVANCE
Coptidis rhizoma, first recorded in the "Shen Nong's Herbal Classic", is one of the traditional Chinese medicine (TCM) used to treat infectious diseases, with reputed effectiveness against oropharyngeal candidiasis (OPC). Studies have demonstrated the inhibitory properties of C. rhizoma (CRE) against Candida albicans, yet there is limited information available regarding its treatment mechanism for OPC.
AIM OF THE STUDY
Our previous research has suggested that CRE can prevent the formation of C. albicans hyphae and their invasion of the oral mucosa, thereby exerting a therapeutic effect on OPC. Nevertheless, the precise therapeutic mechanisms remain incompletely understood. Previous studies have revealed that a receptor for globular heads of C1q (gC1qR), a crucial co-receptor of the epidermal growth factor receptor (EGFR), facilitates the EGFR-mediated internalization of C. albicans. Therefore, this study aims to investigate the potential mechanism of action of CRE and its primary component, berberine (BBR), in treating OPC by exploring their effects on the gC1qR-EGFR co-receptor.
MATERIALS AND METHODS
To identify the chemical components of CRE, we utilized Ultra-high performance liquid chromatography in conjunction with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), revealing the presence of at least 18 distinct components. To observe the therapeutic effects of CRE on OPC at the animal level, we employed hematoxylin and eosin staining, periodic acid-Schiff staining, scanning electron microscopy, and fungal load detection. Subsequently, we evaluated the anti-inflammatory properties of CRE and its main component, BBR, in treating OPC. This was achieved through enzyme-linked immunosorbent assay (ELISA) both at the animal and cellular levels. Additionally, we assessed the ability of C. albicans to disrupt the epithelial barrier of FaDu cells by studying the protective effects of BBR on the fusion barrier using the transwell assay. To further explore the underlying mechanisms, we analyzed the effects of BBR on the gC1qR-EGFR/extracellular signal-regulated kinase/c-Fos signaling pathway at the cellular level using qRT-PCR, western blotting, and immunofluorescence. Furthermore, we validated the effects of BBR on the gC1qR-EGFR co-receptor through ELISA, qRT-PCR, and western blotting. Finally, to confirm the outcomes observed at the cellular level, we validated the impact of CRE on the gC1qR-EGFR co-receptor in vivo using qRT-PCR, western blotting, and immunofluorescence. These comprehensive methods allowed us to gain a deeper understanding of the therapeutic mechanisms of CRE and BBR in treating OPC.
RESULTS
Our findings indicate that CRE and its primary component, BBR, effectively alleviated the symptoms of OPC by modulating the gC1qR-EGFR co-receptor. The chemical composition of CRE and BBR was accurately identified using UPLC-Q/TOF-MS. The gC1qR-EGFR co-receptor plays a crucial role in regulating downstream signaling pathways, emerging as a potential therapeutic target for OPC treatment. Through both in vitro and in vivo experiments, we explored the therapeutic potential of CRE and BBR in OPC. Additionally, we employed overexpression and silencing techniques to confirm that BBR can indeed influence the gC1qR-EGFR co-receptor and regulate the gC1qR-EGFR/extracellular signal-regulated kinase (ERK)/c-Fos signaling pathway, leading to improved OPC outcomes. Furthermore, the significance of CRE's effect on the gC1qR-EGFR co-receptor was validated in vivo.
CONCLUSION
Our study demonstrates that CRE and its main component, BBR, can effectively alleviate OPC symptoms by targeting the gC1qR-EGFR heterodimer receptor. This discovery offers a promising new therapeutic approach for the treatment of OPC.
Topics: ErbB Receptors; Animals; Drugs, Chinese Herbal; Candidiasis, Oral; Candida albicans; Epithelial Cells; Humans; Berberine; Proto-Oncogene Proteins c-fos; Mice; Mouth Mucosa; Antifungal Agents; Male; Cell Line; Signal Transduction; MAP Kinase Signaling System; Coptis chinensis
PubMed: 38729536
DOI: 10.1016/j.jep.2024.118305 -
Journal of the American Chemical Society May 2024Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to...
Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; HBBDC) with double (in 4,4'-stilbenedicarboxylic acid; HSDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise CH/CH sorption isotherms and the corresponding powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.
PubMed: 38726589
DOI: 10.1021/jacs.4c04809 -
Acta Crystallographica. Section E,... Apr 2024The title compound (CHNS, common name: -jasmone 4-ethyl-thio-semicarbazone) was synthesized by the equimolar reaction of -jasmone and 4-ethyl-thio-semicarbazide in...
The title compound (CHNS, common name: -jasmone 4-ethyl-thio-semicarbazone) was synthesized by the equimolar reaction of -jasmone and 4-ethyl-thio-semicarbazide in ethanol facilitated by acid catalysis. There is one crystallographically independent mol-ecule in the asymmetric unit, which shows disorder of the terminal ethyl group of the jasmone carbon chain [site-occupancy ratio = 0.911 (5):0.089 (5)]. The thio-semicarbazone entity [N-N-C(=S)-N] is approximately planar, with the maximum deviation of the mean plane through the N/N/C/S/N atoms being 0.0331 (8) Å, while the maximum deviation of the mean plane through the five-membered ring of the jasmone fragment amounts to -0.0337 (8) Å. The dihedral angle between the two planes is 4.98 (7)°. The mol-ecule is not planar due to this structural feature and the -hybridized atoms of the jasmone carbon chain. Additionally, one H⋯N intra-molecular inter-action is observed, with graph-set motif (5). In the crystal, the mol-ecules are connected through pairs of H⋯S inter-actions with (8) and (7) graph-set motifs into centrosymmetric dimers. The dimers are further connected by H⋯N inter-actions with graph-set motif (12), which are related by an inversion centre, forming a mono-periodic hydrogen-bonded ribbon parallel to the -axis. The crystal structure and the supra-molecular assembly of the title compound are compared with four known -jasmone thio-semicarbazone derivatives (two crystalline modifications of the non-substituted form, the 4-methyl and the 4-phenyl derivatives). A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are from H⋯H (70.7%), H⋯S/S⋯H (13.5%), H⋯C/C⋯H (8.8%), and H⋯N/N⋯H (6.6%) inter-faces (only the disordered atoms with the highest s.o.f. were considered for the evaluation).
PubMed: 38721415
DOI: 10.1107/S2056989024002913 -
Journal of Chemical Theory and... May 2024Long-range electrostatic effects are fundamental for describing chemical reactivity in the condensed phase. Here, we present the methodology of an efficient quantum...
Analytic Gradients for the Electrostatic Embedding QM/MM Model in Periodic Boundary Conditions Using Particle-Mesh Ewald Sums and Electrostatic Potential Fitted Charge Operators.
Long-range electrostatic effects are fundamental for describing chemical reactivity in the condensed phase. Here, we present the methodology of an efficient quantum mechanical/molecular mechanical (QM/MM) model in periodic boundary conditions (PBC) compatible with QM/MM boundaries at chemical bonds. The method combines electrostatic potential fitted charge operators and electrostatic potentials derived from the smooth particle-mesh Ewald (PME) sum approach. The total energy and its analytic first derivatives with respect to QM, MM, and lattice vectors allow QM/MM molecular dynamics (MD) in the most common thermodynamic ensembles. We demonstrate the robustness of the method by performing a QM/MM MD equilibration of methanol in water. We simulate the cis/trans isomerization free-energy profiles in water of proline amino acid and a proline-containing oligopeptide, showing a correct description of the reaction barrier. Our PBC-compatible QM/MM model can efficiently be used to study the chemical reactivity in the condensed phase and enzymatic catalysis.
PubMed: 38712506
DOI: 10.1021/acs.jctc.4c00201 -
Journal of Drugs in Dermatology : JDD May 2024This paper outlines a process undertaken by a physician to design a peptide aimed at impacting the extracellular matrix. From a position of very little expertise, a new...
This paper outlines a process undertaken by a physician to design a peptide aimed at impacting the extracellular matrix. From a position of very little expertise, a new peptide was designed with amino acid constituents based on the structural proteins collagen and elastin. Sequencing was also considered, given the periodic repetition observed in these proteins, and a peptide with reasonable molecular weight and physical characteristics was designed using available software. The sequence of events concerning intellectual property, functionality investigation, and eventual use of the peptide in new formulations is detailed. This may be of interest to physicians who consider this exercise out of the scope of the usual practice. J Drugs Dermatol. 2024;23(5):347-352. doi:10.36849/JDD.7921.
Topics: Humans; Peptides; Drug Design; Elastin; Collagen; Extracellular Matrix; Intellectual Property; Physicians
PubMed: 38709700
DOI: 10.36849/JDD.7921 -
Fish & Shellfish Immunology Jul 2024Crucian carp (Carassius carassius) is an important aquatic economic animal, and the immune barrier function of its intestine has been a focus of research into oral...
Crucian carp (Carassius carassius) is an important aquatic economic animal, and the immune barrier function of its intestine has been a focus of research into oral vaccines and drugs. However, the histological structures of the intestinal barrier and its adjacent areas have not been clearly established, and little subcellular evidence is available to elucidate the spatial distribution of intracellular biological processes. In this study, the spatial distribution of autophagy and endosome formation in the intestinal epithelial cells (IECs) of crucian carp were analyzed. These two biological activities are closely related to intestinal homeostasis, immunity, and cell communication. Periodic acid-Schiff (PAS) and Masson's trichrome staining were employed to elucidate the distinctive histological framework of the Crucian carp's myoid cell network, which resides within the subepithelial layer and is characterized by gap junctions. Transmission electron microscopy (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) were used to detect the structural and functional aspects of the IEC in different intestinal segments. TEM and immunohistochemical analyses captured the biogenesis and maturation of early and late endosomes as well as multivesicular bodies (MVBs), as well as the initiation and progression of autophagy, including macroautophagy and mitophagy. The endosome and MVBs-specific marker CD63 and autophagy-related protein LC3 were highly expressed in IECs and were correlated with autophagy and endosome biosynthesis in the apical and basal regions of individual cells, and differed between different intestinal segments. In summary, this study elucidated the ubiquity and morphological characteristics of autophagy and endosome formation across different intestinal segments of crucian carp. A unique myoid cell network beneath the intestinal epithelium in crucian carp was also identified, expanding the histological understanding of this animal's intestinal tract.
Topics: Animals; Carps; Autophagy; Endosomes; Intestinal Mucosa; Intestines; Epithelial Cells
PubMed: 38704111
DOI: 10.1016/j.fsi.2024.109605 -
Anatomia, Histologia, Embryologia May 2024Snakes represent a wide and diverse group of species and have anatomical particularities, such as the renal sexual segment (RSS), a structure located in the kidneys and...
Snakes represent a wide and diverse group of species and have anatomical particularities, such as the renal sexual segment (RSS), a structure located in the kidneys and formed from the hypertrophy of the urinary ducts and nephrons. This study aims at describing the histological aspects of the RSS of Boa constrictor, Epicrates cenchria and Corallus hortulanus, all of which are Brazilian snake species from the Boidae family. The reproductive system and kidneys of five male specimens of E. cenchria, three male specimens of C. hortulanus and two male specimens of B. constrictor were obtained. Tissue samples were processed histologically and different stains used (Toluidine Blue, Alcian Blue and Periodic Acid Schiff). The histological evaluation of the RSS of E. cenchria, C. hortulanus and B. constrictor shows that the RSS in these species varies when comparing individuals in the reproductive period with those which are not. It also allows for the observation of the segment's secretory activity in animals in the reproductive stage (mature sperm in the lumen of the seminiferous tubules) as well as in those which are not. Finally, the histological evaluation also reveals the variation of the secretion product in individuals in the reproductive period, in those which are not, and also among individuals within the same reproductive stage.
Topics: Animals; Male; Kidney; Brazil; Boidae; Seminiferous Tubules; Spermatozoa
PubMed: 38702901
DOI: 10.1111/ahe.13049