-
Frontiers in Microbiology 2024As a symbiotic probiotic for the host, (CB) has the potential to strengthen the body's immune system and improve intestinal health. However, the probiotic mechanism of...
INTRODUCTION
As a symbiotic probiotic for the host, (CB) has the potential to strengthen the body's immune system and improve intestinal health. However, the probiotic mechanism of CB is not completely understood. The CBX 2021 strain isolated by our team from a health pig independently exhibits strong butyric acid production ability and stress resistance. Therefore, this study comprehensively investigated the efficacy of CBX 2021 in pigs and its mechanism of improving pig health.
METHODS
In this study, we systematically revealed the probiotic effect and potential mechanism of the strain by using various methods such as microbiome, metabolites and transcriptome through animal experiments and cell experiments .
RESULTS
Our study showed that CBX 2021 improved growth indicators such as daily weight gain in weaned piglets and also reduced diarrhea rates. Meanwhile, CBX 2021 significantly increased immunoglobulin levels in piglets, reduced contents of inflammatory factors and improved the intestinal barrier. Subsequently, 16S rRNA sequencing showed that CBX 2021 treatment implanted more butyric acid-producing bacteria (such as ) in piglets and reduced the number of potentially pathogenic bacteria (like ). With significant changes in the microbial community, CBX 2021 improved tryptophan metabolism and several alkaloids synthesis in piglets. Further experiments showed that CBX 2021 adhesion directly promoted the proliferation of a porcine intestinal epithelial cell line (IPEC-J2). Moreover, transcriptome analysis revealed that bacterial adhesion increased the expression of intracellular G protein-coupled receptors, inhibited the Notch signaling pathway, and led to a decrease in intracellular pro-inflammatory molecules.
DISCUSSION
These results suggest that CBX 2021 may accelerate piglet growth by optimizing the intestinal microbiota, improving metabolic function and enhancing intestinal health.
PubMed: 38946904
DOI: 10.3389/fmicb.2024.1394332 -
Surgery Open Science Aug 2024A grading system was developed for computerized tomography (CT) scans evaluating patients with suspected small bowel obstruction (SBO). We hypothesized that patients...
BACKGROUND
A grading system was developed for computerized tomography (CT) scans evaluating patients with suspected small bowel obstruction (SBO). We hypothesized that patients with a higher grade of suspected SBO on CT scan would be more likely to require surgical intervention.
METHODS
Retrospective chart review of patients who presented to the Emergency Room (ER) who had a CT of the abdomen and pelvis for suspected SBO. Patients were divided into 5 groups: Grade 1 (SBO unlikely), Grade 2 (probable partial or early SBO), Grade 3 (probable high grade SBO), Grade 4 (SBO with changes concerning for ischemia) and Not Graded.
RESULTS
The CT scans of 655 patients were graded. Of the 22 patients with a grade 1 SBO, only 1 went for surgery (4.5 %). For grade 2 patients, 23 out of 299 had an operation (7.7 %), for grade 3 it was 84 out of 299 (28.1 %) and for grade 4 SBO, 25 out of 35 patients (71.4 %) had surgery. The value is <0.00001. The three most common intraoperative findings were SBO obstruction from adhesions alone (48 % of cases), followed by incarcerated hernias (12 %) and ischemic bowel (9 %). Only 8 cases out of 133 operations (6 % of total) had no findings at time of surgery other than dilated bowel.
CONCLUSIONS
The CT grading scale for SBO developed at our institution shows excellent correlation between grade and going for surgery, with few negative results, and can be a useful tool among other factors for general surgeons when deciding whether or not to operate on a patient with suspected SBO.
PubMed: 38946861
DOI: 10.1016/j.sopen.2024.05.016 -
World Journal of Clinical Oncology Jun 2024Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on...
BACKGROUND
Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures.
AIM
To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research.
METHODS
We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide.
RESULTS
Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence.
CONCLUSION
Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.
PubMed: 38946828
DOI: 10.5306/wjco.v15.i6.765 -
Biomedical Engineering Letters Jul 2024Degradable piezoelectric materials possess significant potential for application in the realm of bone tissue regeneration. However, the correlation between cell...
Degradable piezoelectric materials possess significant potential for application in the realm of bone tissue regeneration. However, the correlation between cell regulation mechanisms and the dynamic variation caused by material degradation has not been explained, hindering the optimization of material design and its in vivo application. Herein, piezoelectric poly (L-lactic acid) (PLLA) nanofibers with different molecular weights (MW) were fabricated, and the effects of their piezoelectric properties, structural morphology, and material products during degradation on the adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) were investigated. Our results demonstrated that cell adhesion-mediated piezoelectric stimulation could significantly enhance cell spreading, cell orientation, and upregulate the expression of calmodulin, which further triggers downstream signaling cascade to regulate osteogenic differentiation markers of type I collagen and runt-related transcription factor 2. Additionally, during the degradation of the nanofibers, the piezoelectric properties of PLLA weakened, the fibrous structure gradually diminished, and pH levels in the vicinity decreased, which resulting in reduced osteogenic differentiation capability of MSCs. However, nanofibers with higher MW (280 kDa) have the ability to maintain the fibrous morphology and piezoelectricity for a longer time, which can regulate the osteogenic differentiation of stem cells for more than 4 weeks. These findings have provide a new insight to correlate cell behavior with MW and the biodegradability of piezopolymers, which revealed an active method for cell regulation through material optimization for bone tissue engineering in near future.
PubMed: 38946806
DOI: 10.1007/s13534-024-00374-3 -
Journal of Cell Communication and... Jun 2024The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly... (Review)
Review
The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.
PubMed: 38946720
DOI: 10.1002/ccs3.12027 -
Advanced Science (Weinheim,... Jul 2024Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within...
Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.
PubMed: 38946588
DOI: 10.1002/advs.202403640 -
Journal of Indian Prosthodontic Society Jul 2024This study investigates the interaction of zirconia and polyetheretherketone (PEEK) with indirect composite in fixed dental prostheses. This investigation aimed to... (Comparative Study)
Comparative Study
Comparative evaluation of bond strength and color stability of polyetheretherketone and zirconia layered with indirect composite before and after thermocycling: An in vitro study.
AIM
This study investigates the interaction of zirconia and polyetheretherketone (PEEK) with indirect composite in fixed dental prostheses. This investigation aimed to assess the shear bond strength (SBS) and color stability of zirconia and PEEK before and after aging, addressing critical concerns in dental restorative applications.
SETTINGS AND DESIGN
The current in vitro study used 96 samples, 48 of which were divided into two groups, zirconia and PEEK, before and after thermocycling. A dual-axis chewing simulator was used for thermocycling. SBS was measured using a universal testing machine, and color stability was checked using a reflective spectrophotometer.
MATERIALS AND METHODS
Ninety-six samples were categorized into zirconia and PEEK groups, each with subgroups undergoing thermocycling. Samples were prepared using computer-aided design/computer-aided manufacturing milling and veneered with composite resin. Thermocycling involved 10,000 cycles, simulating stress levels equivalent to approximately 1 year of clinical use. SBS was assessed using standardized tests. Stereomicroscopic analysis was performed to evaluate the type of failure. Color stability of the core materials with indirect composite was done using a spectrophotometer before and after aging.
STATISTICAL ANALYSIS USED
Statistical analysis included paired t-tests and independent t-tests in SPSS software.
RESULTS
The results revealed that SBS values for composite on PEEK decreased from 13.86 ± 0.164 MPa before thermocycling to 13.46 ± 0.185 MPa after thermocycling, with a significant difference (P < 0.005). However, both pre- and postthermocycling values for PEEK were higher than zirconia. The t-test confirmed the lower bond strength of composite to zirconia, with a noteworthy improvement after aging. Stereomicroscopic images revealed adhesive failure for the zirconia group and mixed (adhesive and cohesive) failure for the PEEK group. ΔE values were 3.21 ± 0.127 and 2.93 ± 0.142 for zirconia and PEEK groups, respectively (P < 0.005).
CONCLUSION
Within the limitations of this study, it can be deduced that PEEK is a feasible substitute for zirconia when used in conjunction with indirect composite for the fabrication of dental prostheses.
Topics: Benzophenones; Zirconium; Ketones; Polyethylene Glycols; Polymers; Composite Resins; In Vitro Techniques; Dental Bonding; Color; Materials Testing; Shear Strength; Dental Materials; Dental Stress Analysis; Humans
PubMed: 38946508
DOI: 10.4103/jips.jips_36_24 -
Expert Opinion on Therapeutic Patents Jul 2024Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as... (Review)
Review
Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Here, we updated an overview of design, synthesis and structure - activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.
PubMed: 38946486
DOI: 10.1080/13543776.2024.2368742 -
Nihon Yakurigaku Zasshi. Folia... 2024Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular... (Review)
Review
[Pharmacological properties and clinical development overview of pertuzumab (genetical recombination), trastuzumab (genetical recombination) and vorhyaluronidase alfa (genetical recombination) (PHESGO combination for subcutaneous injection MA, IN)].
Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular HER2 signaling additively or synergistically. Their combination is widely recommended worldwide and has been established as a standard of care for HER2-positive breast cancer. However, improvement is required because of the prolonged time of intravenous infusion. Vorhyaluronidase alfa (rHuPH20) depolymerizes hyaluronan in the subcutaneous connective tissue. It's reported to increase the permeability and absorption levels of drugs. PHESGO combination for subcutaneous injection MA/IN (PHESGO) is a fixed-dose combination of pertuzumab, trastuzumab, and rHuPH20. A confirmatory phase III study (FeDeriCa) was conducted following a dose-finding phase I study (BO30185). Patients with HER2-positive early breast cancer were randomly assigned to receive either intravenous infusion of pertuzumab and trastuzumab or subcutaneous injection of PHESGO, in combination with chemotherapy, to compare the pharmacokinetics (PK), efficacy and safety. A phase II study (PHranceSCa) was also conducted to assess patients' preference and satisfaction. Based on these results, population PK analysis, and other data, PHESGO obtained marketing approval in Japan in September 2023 with indications for "HER2-positive breast cancer" and "advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection". By reducing the administration time, PHESGO is expected to contribute to various needs of patients and improvement of their daily lives. Since drug preparation is not required, it can provide convenience to healthcare professionals, leading to stress reduction of medical resources as well.
Topics: Humans; Trastuzumab; Antibodies, Monoclonal, Humanized; Hyaluronoglucosaminidase; Injections, Subcutaneous; Breast Neoplasms; Drug Combinations; Clinical Trials as Topic; Receptor, ErbB-2; Female; Recombinant Proteins; Cell Adhesion Molecules
PubMed: 38945908
DOI: 10.1254/fpj.24022 -
Biological & Pharmaceutical Bulletin 2024Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D)...
Suppression of the Epithelial-Mesenchymal Transition and Maintenance of the Liver Functions in Primary Hepatocytes through Dispersion Culture within a Dome-Shaped Collagen Matrix.
Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D) environment, primary hepatocytes undergo rapid dedifferentiation via an epithelial-mesenchymal transition (EMT) and lose their liver-specific functions. On the other hand, a three-dimensional (3D) culture of primary hepatocyte organoids presents challenges for analyzing cellular functions and molecular behaviors due to strong cell-cell adhesion among heterogeneous cells. In this study, we developed a novel dispersion culture method of hepatocytes within a dome-shaped collagen matrix, overcoming conventional limitations. The expression levels of EMT-related genes were lower in rat primary hepatocytes cultured using this method for 4 d than in cells cultured using the 2D method. Furthermore, albumin production, a marker of liver function, declined sharply in rat primary hepatocytes cultured in two dimensions from 6.40 µg/mL/48 h on day 4 to 1.35 µg/mL/48 h on day 8, and declined gradually from 4.92 µg/mL/48 h on day 8 to 3.89 µg/mL/48 h on day 14 in rat primary hepatocytes cultured using our new method. These findings indicate that the newly developed culture method can suppress EMT and maintain liver functions for 14 d in rat primary hepatocytes, potentially expanding the utility of primary hepatocyte cultured by using conventional 3D methods.
Topics: Animals; Hepatocytes; Epithelial-Mesenchymal Transition; Cells, Cultured; Collagen; Male; Liver; Rats; Cell Culture Techniques; Rats, Sprague-Dawley; Albumins
PubMed: 38945897
DOI: 10.1248/bpb.b24-00180