Search

In this study, Akkermansia muciniphila (Akk) was cultured to a concentration of more than 109 CFU/mL in optimized liquid thioglycolate medium. Besides, the differential metabolites in the fermentation supernatants from the original and optimized medium were analyzed by non-targeted metabolomics, and the physiological functions of the characteristic products were evaluated. The results showed that when cultured in the optimized medium, Akk produced higher amounts of various functional metabolites such as propionic acid, bardoxifene, docetaxel and vinblastine by affecting protein digestion and absorption, aminoacyl tRNA biosynthesis, bile secretion, ATP-binding cassette (ABC) transporter, and the metabolic pathways of amino acid biosynthesis. These metabolites could be directly related to anti-cancer, anti-inflammatory, anti-obese and other functions. This study provides solid evidence that Akk can function as a probiotic agent and postbiotic to regulate many diseases, and lays a theoretical foundation for future industrial production.

Diabetes is a metabolic disease characterized by insulin secretion disorder. When serious, it can cause various complications (cardiovascular and cerebrovascular diseases, cataract and other eye diseases, kidney disease and cancer), bringing a huge economic burden to the society and families and torturing patients. The risk of diabetes is not only related to genes, living pressure and working environment, but also directly related to patients’ lifestyles and dietary habits. An unhealthy diet (high in fat and sugar) can induce the intestinal flora to produce adverse metabolites, which can in turn promote the occurrence and development of diabetes. Intestinal flora imbalance is widespread in the pathogenesis of various types of diabetes. As an important factor influencing the intestinal flora, diet is not only essential to maintain body functions, but also can contribute to intestinal immunity. Regulation of the intestinal environment through diet is expected to be an effective preventive means and auxiliary therapy for diabetes. By synthesizing the existing literature, this article discusses the features of the intestinal flora and the mechanism of the effect of diet-mediated regulation of the intestinal flora on diabetes based on systematic medical theory, and reviews the role scientific diet plays in regulating intestinal homeostasis and immunity and consequently reducing the incidence and complications of diabetes. We hope that this review will provide a basis for early diagnosis and prevention and adjuvant treatment of diabetes.

Objective The endoscopic endonasal approach has emerged as an excellent option for the treatment of lesions involving the petroclival fissure (PCF). Here, we investigate the surgical anatomy of the ventral PCF and its application in endoscopic endonasal surgery. Methods Sixteen head specimens were used to investigate the anatomical features of PCF and relevant technical nuances in translacerum, extreme medial, and contralateral transmaxillary (CTM) approaches. Two representative endoscopic endonasal surgeries involving the PCF were selected to illustrate the clinical application. Results From the endoscopic endonasal view, the ventral PCF is presented as a lazy L sign, which is divided into two distinct segments: (1) upper (or petrosphenoidal) segment, which extends vertically from the foramen lacerum inferiorly to the junction of the petrosal process of sphenoid bone and petrous apex superiorly, and (2) lower (or petroclival) segment, which extends inferolaterally from the foramen lacerum to the ventral jugular foramen. Approaching both segments of the ventral PCF first requires full exposure of the foramen lacerum, followed either by exposure of the anterior wall of cavernous sinus and paraclival internal carotid artery for upper segment access, or transection of pterygosphenoidal fissure and Eustachian tube mobilization for lower segment access. Combined with a CTM approach, the lateral extension of the surgical access can be improved for both upper and lower segment PCF approaches. Conclusion This study provides a detailed investigation of the microsurgical anatomy of the ventral part of PCF, relevant surgical approaches, and technical nuances that may facilitate its safe exposure intraoperatively. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scars (HS) are dermal diseases characterized by excessive fibroblast proliferation and collagen deposition following burns or trauma. While Tenascin-C (TNC)'s role in promoting visceral fibrosis has been established, its impact on skin tissue fibrosis remains unclear. This study aims to investigate the effects of TNC on HS. Methods: RNA sequence and IHC techniques were used to examine the upregulation of TNC gene in human hypertrophic scar tissue compared to normal tissues. Knockdown of TNC in Human skin fibroblasts (HFF-1) cells was achieved, and expression of Col1 and Col3 was evaluated using qPCR. Sirius red collagen staining assessed impact on total collagen content and ECM deposition. Effects on cell proliferation and migration were investigated through cck-8 and cell scratch experiments. Lentivirus infection was used to knock out TNC, and resulting samples were injected into ear wound of rabbits. Effects of TNC knockout on ear scar formation were measured using digital morphology, ultrasound, SEI, H&E, and Masson trichrome methods. Results: Cell experiments: downregulation of TNC decreased Col1 and Col3 expression, leading to reduced collagen production and extracellular matrix deposition. It did not affect HFF-1 cell proliferation and migration. Animal experiments: TNC knockdown promoted wound healing and reduced collagen deposition in rabbit ears. Conclusion: This study suggests that knocking down TNC inhibits collagen formation and extracellular matrix deposition, thereby inhibiting hypertrophic scar formation. Therefore, TNC can be considered a potential biomarker for HS formation and may offer promising treatment strategies for clinical management of hypertrophic scars. [ABSTRACT FROM AUTHOR]

Objective: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. Methods: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). Results: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1β and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. Conclusions: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA. [ABSTRACT FROM AUTHOR]

The striatin-interacting phosphatase and kinase (STRIPAK) complexes integrate extracellular stimuli that result in intracellular activities. Previously, we discovered that STRIPAK is a key machinery responsible for loss of the Hippo tumor suppressor signal in cancer. Here, we identified the Hippo-STRIPAK complex as an essential player in the control of DNA double-stranded break (DSB) repair and genomic stability. Specifically, we found that the mammalian STE20-like protein kinases 1 and 2 (MST1/2), independent of classical Hippo signaling, directly phosphorylated zinc finger MYND type-containing 8 (ZMYND8) and hence resulted in the suppression of DNA repair in the nucleus. In response to genotoxic stress, the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway was determined to relay nuclear DNA damage signals to the dynamic assembly of Hippo-STRIPAK via TANK-binding kinase 1-induced (TBK1-induced) structural stabilization of the suppressor of IKBKE 1- sarcolemma membrane-associated protein (SIKE1-SLMAP) arm. As such, we found that STRIPAK-mediated MST1/2 inactivation increased the DSB repair capacity of cancer cells and endowed these cells with resistance to radio- and chemotherapy and poly(ADP-ribose)polymerase (PARP) inhibition. Importantly, targeting the STRIPAK assembly with each of 3 distinct peptide inhibitors efficiently recovered the kinase activity of MST1/2 to suppress DNA repair and resensitize cancer cells to PARP inhibitors in both animal- and patient-derived tumor models. Overall, our findings not only uncover what we believe to be a previously unrecognized role for STRIPAK in modulating DSB repair but also provide translational implications of cotargeting STRIPAK and PARP for a new type of synthetic lethality anticancer therapy., Introduction DNA double-stranded breaks (DSBs) constitute the most deleterious threat to genomic integrity, and the repair of DNA is essential for normal cell growth and animal development (1). Altered DNA [...]

This article, published in the Journal of Neurological Surgery, explores the pterygoid-sphenoidal fissure (PSF) as a key landmark for accessing the foramen lacerum in pediatric endoscopic endonasal surgery. The study evaluates the morphometry and developmental variations of the PSF in a general pediatric population using computed tomography scans. The results show that the length, width, and morphology of the PSF vary significantly across different age groups. Understanding these radiological findings is important for preoperative planning and intraoperative guidance in pediatric endoscopic endonasal surgery. [Extracted from the article]

This article discusses seven different techniques for pituitary transposition in endoscopic endonasal surgery. The techniques are categorized based on their relationship with the dura mater and include extradural, hybrid extradural/intradural, interdural transcavernous, extended interdural transcavernous, intradural hemitransposition, intradural, and pituitary sacrifice. The article evaluates the clinical application and selection of these techniques in different anatomical regions and types of pathology. The authors emphasize the importance of selecting the most appropriate technique based on the specific case and preoperative pituitary function for successful surgical outcomes. [Extracted from the article]

This article, published in the Journal of Neurological Surgery, explores the microsurgical anatomy of the "true" petrous apex and the feasibility of accessing it through the endoscopic endonasal approach. The study conducted detailed dissections of post-mortem human specimens and identified key anatomical landmarks and neurovascular structures. The authors found that the endoscopic endonasal petrosectomy approach provides access to the "true" petrous apex, with two variants based on its relationship with the internal carotid artery. The study concludes that this approach is an effective surgical alternative for accessing lesions in this region. [Extracted from the article]

The article discusses the extreme lateral supracerebellar infratentorial and transtentorial (ELSIT) approach for accessing lesions in the ambient cistern, a challenging area due to its deep location and vital neurovascular structures. The study conducted a systematic dissection on post-mortem human specimens to investigate the anatomical landmarks and measurements of this approach. The ELSIT approach provides a narrow corridor leading to the ambient cistern, with specific landmarks such as the superior petrous vein and posterior root of the trigeminal nerve. Understanding these anatomical nuances is crucial for optimizing surgical outcomes and minimizing complications. [Extracted from the article]

This article, published in the Journal of Neurological Surgery, discusses a case presentation of a 2-year-old boy with a tubero-infundibular craniopharyngioma. The boy had a history of previous surgeries and developed visual abnormalities due to the growth of the tumor. The authors used an endoscopic endonasal transplanum approach to completely remove the tumor, resulting in improvement of visual symptoms. However, the patient did develop diabetes insipidus postoperatively. The article provides valuable insights into the treatment of pediatric patients with craniopharyngioma. [Extracted from the article]

This article discusses the surgical anatomy of the transmastoid transcervical intradural approach to the jugular foramen, which is a challenging area for skull base surgeons due to the presence of critical structures. The approach is versatile and allows for modifications to tailor it to specific tumors. The article provides a detailed description of the surgical steps and relevant anatomy, including variations such as vertebral artery transposition and facial nerve rerouting. The transmastoid transcervical intradural approach provides excellent exposure to the jugular foramen and surrounding areas, but precise knowledge of the anatomy is crucial due to the complex relationships of vital structures in this region. [Extracted from the article]

Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress‐regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy. [ABSTRACT FROM AUTHOR]

The three principal fates of axillary meristem in flowering plants are growth (G), reproduction (R), and inactivity (I). The allocation relationships between each meristem and plant size in annual herbaceous plants tend to change with altered precipitation (P) patterns in arid and semiarid grasslands. Here, we examined the allometry and plasticity of meristem allocation in three dominant annual herbaceous plants: Setaria viridis, Corispermum macrocarpum, and Bassia dasyphylla in a semiarid sandy grassland in northern China. We determined the range of plant sizes for each of the three species in the following treatments: ambient environment (Amb), P increased by 30% (P[+]) and by 60% (P[++]), P decreased by 30% (P[−]) and by 60% (P[− −]), drought for 46 days from May 1st to June 15th (D1) and from July 1st to August 15th (D2). We found that meristem allocation to branching intensity increased while allocation to apical dominance decreased with increasing plant size under decreased precipitation and seasonal drought. Decreased precipitation and seasonal drought caused the slope of allometry of meristem allocation in the three species to be significantly different from 1. Plasticity of meristem allocation to G, R, and I in S. viridis tended to be significantly greater in August under P(+) and P(++) while in C. macrocarpum tended to be greater in July under P(−), P(− −), D1, and D2. Our findings are important components of an adaptive strategy in annual herbaceous plants throughout the development stage, which will contribute to predict their developmental dynamics in the semiarid sandy grassland under future climate change. [ABSTRACT FROM AUTHOR]

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44−CXCR2− neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics. [ABSTRACT FROM AUTHOR]

Aims Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. Methods and results A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE −/− mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum -induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum -induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. Conclusions PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum -promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis. [ABSTRACT FROM AUTHOR]

Drought seriously endangers the development of agro‐pastoral ecotone in arid and semi‐arid regions. However, drought evolution characteristics of semi‐arid sandy grassland and its drivers are not well understood in the complex climate change context. Thus, in this paper, the revised standardized precipitation evaporation indices on one‐month (SPEI‐1) and growing‐season (SPEI‐6) scale, flash drought and dry spells (DS) were calculated as drought indicators, and the temporal variabilities and meteorological drivers of drought in Horqin Sandy Land during the growing period (April–September) from 2007 to 2021 were studied. The results showed that SPEI‐1 and SPEI‐6 exhibited negative trends and periodic change. This drought aggravation was manifested in increased grades and numbers of drought months. Flash droughts can occur every month during the growing season. And its occurrence was not only positively correlated with all drought events in frequency but also synchronized in time. The increased number of DS showed an asymmetrical shift towards 7‐day‐and‐longer DS. SPEI sensitivity to precipitation (P) was noticeably higher than to atmospheric evapotranspiration demand (AED) at both monthly and growing season scales. SPEI sensitivity to AED was modulated by P amounts, which was higher during low P period. Apart from the amounts of P and AED, their temporal variability also strongly determined how they affect the drought severity. P was also the main driver for flash drought and long DS, but AED with larger amount and higher variability is the reason for their aggravation. Our results demonstrate the complexity of drought intensification in semi‐arid sandy grasslands and highlight the important role of AED anomalies in it. [ABSTRACT FROM AUTHOR]

Enamel possesses ingenious hierarchical structure that gives rise to superior fracture resistance. Despite considerable efforts devoted to characterization of fracture behavior of enamel, the role of rod decussation in fracture of enamel is largely unknown. In this study, the features of rod decussation in the inner enamel are experimentally identified, and analyses of crack growth in enamel are carried out using a micromechanical model of enamel, in which the structural features of the outer enamel and rod decussation of the inner enamel are incorporated. We carry out calculations within a framework based on the extended finite element method, and the crack growth and crack path selection are natural outcomes of imposed loading. We show that crack deflection in enamel is controlled by rod decussation. For crack growth in the parazone, the crack path is oriented along the axis of enamel rods, leading to gross crack deflection. The microstructure of inner enamel with intermediate inclination angle enables multiple crack deflections, giving rise to enhanced toughness. For crack growth in the diazone, the transition in orientation of crack deflection occurs as inclination angle increases. The relatively straight crack path emerges in the case of the microstructure of enamel with intermediate inclination angle, leading to weak fracture resistance. It is further found that compared with the diazone, the gross crack deflection in the parazone provides greater contribution to fracture resistance of enamel. The findings of this study provide a good mechanistic understanding of the role of rod decussation in enamel. [ABSTRACT FROM AUTHOR]