Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism.

Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.

The status of intimate partner violence against pregnant women in contemporary China: a scoping review.

PURPOSE: This review explored the status of publications on intimate partner violence (IPV) against pregnant women in contemporary China. METHODS: The PubMed, Cochrane Library, Embase, CINAHL, and PsycInfo databases were searched using the terms "IPV," "pregnant woman," "Chinese," and synonyms in English, along with related keywords for Chinese publications. All literature pertaining to IPV during pregnancy, conducted in China, and published between 1987 and September 2023 was included. RESULTS: A total of 37 articles from 30 studies were selected. The prevalence of IPV during pregnancy ranged from 2.5% to 31.3%, with psychological violence being the most common form. Frequently identified risk factors included unintended pregnancy, poor family economic conditions, male partners engaging in health risk behaviors, poor employment status of women or their partners, low education levels among women, physical or mental health issues, strained couple relationships, and in-law conflicts. IPV during pregnancy primarily led to mental health problems for the victims and could result in adverse obstetric outcomes, as well as negative effects on the temperament and development of the offspring. Victims in China demonstrated a low willingness to seek help from professionals. Furthermore, relevant research in mainland China is scarce, with a limited number of studies and non-standardized research methodologies. CONCLUSION: Future research should investigate IPV in pregnancy from various perspectives, identify factors unique to IPV during pregnancy, and focus on high-risk groups. Considering the conditions in China, there is a pressing need to increase public awareness of IPV and to investigate interventions aimed at addressing this issue.

Cyclic stretch induced epigenetic activation of periodontal ligament cells.

Periodontal ligament (PDL) cells play a crucial role in maintaining periodontal integrity and function by providing cell sources for ligament regeneration. While biophysical stimulation is known to regulate cell behaviors and functions, its impact on epigenetics of PDL cells has not yet been elucidated. Here, we aimed to investigate the cytoskeletal changes, epigenetic modifications, and lineage commitment of PDL cells following the application of stretch stimuli to PDL. PDL cells were subjected to stretching (0.1 Hz, 10 %). Subsequently, changes in focal adhesion, tubulin, and histone modification were observed. The survival ability in inflammatory conditions was also evaluated. Furthermore, using a rat hypo-occlusion model, we verified whether these phenomena are observed in vivo. Stretched PDL cells showed maximal histone 3 acetylation (H3Ace) at 2 h, aligning perpendicularly to the stretch direction. RNA sequencing revealed stretching altered gene sets related to mechanotransduction, histone modification, reactive oxygen species (ROS) metabolism, and differentiation. We further found that anchorage, cell elongation, and actin/microtubule acetylation were highly upregulated with mechanosensitive chromatin remodelers such as H3Ace and histone H3 trimethyl lysine 9 (H3K9me3) adopting euchromatin status. Inhibitor studies showed mechanotransduction-mediated chromatin modification alters PDL cells behaviors. Stretched PDL cells displayed enhanced survival against bacterial toxin (C12-HSL) or ROS (H2O2) attack. Furthermore, cyclic stretch priming enhanced the osteoclast and osteoblast differentiation potential of PDL cells, as evidenced by upregulation of lineage-specific genes. In vivo, PDL cells from normally loaded teeth displayed an elongated morphology and higher levels of H3Ace compared to PDL cells with hypo-occlusion, where mechanical stimulus is removed. Overall, these data strongly link external physical forces to subsequent mechanotransduction and epigenetic changes, impacting gene expression and multiple cellular behaviors, providing important implications in cell biology and tissue regeneration.

Strontium/Silicon/Calcium-Releasing Hierarchically Structured 3D-Printed Scaffolds Accelerate Osteochondral Defect Repair.

Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self-healing capacity and damaging bone structures. To tackle this problem, a scaffold-mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε-caprolactone) and strontium (Sr)-doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn-embedded scaffolds (SrBGn-µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation-related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow-derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn-µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.

Human neural stem cell secretome relieves endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after traumatic brain injury in a rat model.

Neural stem cell secretome (NSC-S) plays an important role in neuroprotection and recovery. Studies have shown that endoplasmic reticulum stress (ER stress) is involved in the progression of traumatic brain injury (TBI) and is a crucial cause of secondary damage and neuronal death after brain injury. Whether NSC-S is engaged in ER stress and ER stress-mediated neuronal apoptosis post-TBI has not been investigated. In the study, the Feeney SD male rat model was established. The results showed that NSC-S treatment significantly improved the behavior of rats with TBI. In addition, NSC-S relieved ER stress in TBI rats and was observed by transmission electron microscopy and western blot. The specific mechanism was further elucidated that restoration was achieved by alleviating the PERK-eIF2α pathway and thus protecting neurons from apoptosis. Notably, the discovery of calumenin (CALU) in NSC-S by liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) may be related to the protective effect of NSC-S on ER stress in neurons. Also, the mechanism by which it functions may be related to ubiquitination. In summary, NSC-S improved prognosis and ER stress in TBI rats and might be a promising treatment for relieving TBI.

Development of an Injectable Biphasic Hyaluronic Acid-Based Hydrogel With Stress Relaxation Properties for Cartilage Regeneration.

Biomimetic stress-relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress-relaxing hyaluronic acid (HA)-based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress-relaxing hydrogels (τ1/2; SR50, 60-2000 s) are successfully prepared at ≈3 kPa stiffness with self-healing and shear-thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress-relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress-relaxing HA-based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration.

Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids.

Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross-species differences in animal models. Here, a human midbrain model is established that uses hiPSC-derived midbrain organoids to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single-cell level.

Serial mediating effects of childhood trauma and conduct behaviors on the impact of family history among patients with alcohol use disorder.

Family history (FH) of alcoholism increases the risk of alcohol use disorder (AUD); however, the contribution of childhood trauma (CT) in this respect remains unclear. This study investigated the relationship between FH and AUD-related clinical characteristics (social onset, antisocial tendency, and severity of problematic alcohol consumption) through the mediating effects of childhood trauma (CT) and conduct behaviors (CB) in a Korean male population with AUD. A total of 304 patients hospitalized for AUD at 16 psychiatric hospitals completed standardized questionnaires, including self-rated scales. Mediation analyses were performed using the SPSS macro PROCESS. Individuals with positive FH (133, 44%) had greater CT and CB and more severe AUD-related clinical characteristics than those without FH (171, 56%). In the present serial mediation model, FH had significant direct and indirect effects on AUD-related clinical characteristics through CT and CB. Indirect effects were 21.3% for social onset, 46.3%, antisocial tendency, and 37.9% for problematic drinking. FH directly contributed to AUD-related clinical characteristics, and CT and CB played mediating roles. This highlights the importance of careful intervention and surveillance of adverse childhood experiences and conduct disorder to prevent and mitigate alcohol-related problems in individuals with FH of AUD.

The Neuroprotective Effect of Therapeutic Hypothermia in Cognitive Impairment of an Ischemia/Reperfusion Injury Mouse Model.

Background and Objectives: Therapeutic hypothermia (TH) shows promise as an approach with neuroprotective effects, capable of reducing secondary brain damage and intracranial pressure following successful mechanical thrombectomy in the acute phase. However, its effect on cognitive impairment remains unclear. This study investigated whether TH can improve cognitive impairment in a mouse model of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R). Materials and Methods: Nine-week-old C57BL/6N mice (male) were randomly assigned to three groups: sham, tMCAO/R, and tMCAO/R with TH. Cognitive function was assessed 1 month after model induction using the Y-maze test, and regional cerebral glucose metabolism was measured through positron emission tomography with fluorine-18 fluorodeoxyglucose. Results: tMCAO/R induced cognitive impairment, which showed improvement with TH. The TH group exhibited a significant recovery in cerebral glucose metabolism in the thalamus compared to the tMCAO/R group. Conclusions: These findings indicate that TH may hold promise as a therapeutic strategy for alleviating ischemia/reperfusion-induced cognitive impairment.

Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.

Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

In Vivo Osteogenic and Angiogenic Properties of a 3D-Printed Isosorbide-Based Gyroid Scaffold Manufactured via Digital Light Processing.

INTRODUCTION: Osteogenic and angiogenic properties of synthetic bone grafts play a crucial role in the restoration of bone defects. Angiogenesis is recognised for its support in bone regeneration, particularly in larger defects. The objective of this study is to evaluate the new bone formation and neovascularisation of a 3D-printed isosorbide-based novel CSMA-2 polymer in biomimetic gyroid structures. METHODS: The gyroid scaffolds were fabricated by 3D printing CSMA-2 polymers with different hydroxyapatite (HA) filler concentrations using the digital light processing (DLP) method. A small animal subcutaneous model and a rat calvaria critical-size defect model were performed to analyse tissue compatibility, angiogenesis, and new bone formation. RESULTS: The in vivo results showed good biocompatibility of the 3D-printed gyroid scaffolds with no visible prolonged inflammatory reaction. Blood vessels were found to infiltrate the pores from day 7 of the implantation. New bone formation was confirmed with positive MT staining and BMP-2 expression, particularly on scaffolds with 10% HA. Bone volume was significantly higher in the CSMA-2 10HA group compared to the sham control group. DISCUSSION AND CONCLUSIONS: The results of the subcutaneous model demonstrated a favourable tissue response, including angiogenesis and fibrous tissue, indicative of the early wound healing process. The results from the critical-size defect model showcased new bone formation, as confirmed by micro-CT imaging and immunohistochemistry. The combination of CSMA-2 as the 3D printing material and the gyroid as the 3D structure was found to support essential events in bone healing, specifically angiogenesis and osteogenesis.

Targeting Nuclear Mechanics Mitigates the Fibroblast Invasiveness in Pathological Dermal Scars Induced by Matrix Stiffening.

Pathological dermal scars such as keloids present significant clinical challenges lacking effective treatment options. Given the distinctive feature of highly stiffened scar tissues, deciphering how matrix mechanics regulate pathological progression can inform new therapeutic strategies. Here, it is shown that pathological dermal scar keloid fibroblasts display unique metamorphoses to stiffened matrix. Compared to normal fibroblasts, keloid fibroblasts show high sensitivity to stiffness rather than biochemical stimulation, activating cytoskeletal-to-nuclear mechanosensing molecules. Notably, keloid fibroblasts on stiff matrices exhibit nuclear softening, concomitant with reduced lamin A/C expression, and disrupted anchoring of lamina-associated chromatin. This nuclear softening, combined with weak adhesion and high contractility, facilitates the invasive migration of keloid fibroblasts through confining matrices. Inhibiting lamin A/C-driven nuclear softening, via lamin A/C overexpression or actin disruption, mitigates such invasiveness of keloid fibroblasts. These findings highlight the significance of the nuclear mechanics of keloid fibroblasts in scar pathogenesis and propose lamin A/C as a potential therapeutic target for managing pathological scars.

Selective Suppression of Integrin-Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration.

Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin-mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension-dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin αvß3 and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell-substrate interfaces. This data reveals that integrin-mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures.

Nanozyme-Engineered Hydrogels for Anti-Inflammation and Skin Regeneration.

Inflammatory skin disorders can cause chronic scarring and functional impairments, posing a significant burden on patients and the healthcare system. Conventional therapies, such as corticosteroids and nonsteroidal anti-inflammatory drugs, are limited in efficacy and associated with adverse effects. Recently, nanozyme (NZ)-based hydrogels have shown great promise in addressing these challenges. NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels. The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation. This review highlights the current state of the art in NZ-engineered hydrogels (NZ@hydrogels) for anti-inflammatory and skin regeneration applications. It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness. Additionally, the challenges and future directions in this ground, particularly their clinical translation, are addressed. The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels, offering new possibilities for targeted and personalized skin-care therapies.

Biosubstitutes for dural closure: Unveiling research, application, and future prospects of dura mater alternatives.

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.

Lithium-loaded GelMA-Phosphate glass fibre constructs: Implications for astrocyte response.

Combinations of different biomaterials with their own advantages as well as functionalization with other components have long been implemented in tissue engineering to improve the performance of the overall material. Biomaterials, particularly hydrogel platforms, have shown great potential for delivering compounds such as drugs, growth factors, and neurotrophic factors, as well as cells, in neural tissue engineering applications. In central the nervous system, astrocyte reactivity and glial scar formation are significant and complex challenges to tackle for neural and functional recovery. GelMA hydrogel-based tissue constructs have been developed in this study and combined with two different formulations of phosphate glass fibers (PGFs) (with Fe3+ or Ti2+ oxide) to impose physical and mechanical cues for modulating astrocyte cell behavior. This study was also aimed at investigating the effects of lithium-loaded GelMA-PGFs hydrogels in alleviating astrocyte reactivity and glial scar formation offering novel perspectives for neural tissue engineering applications. The rationale behind introducing lithium is driven by its long-proven therapeutic benefits in mental disorders, and neuroprotective and pronounced anti-inflammatory properties. The optimal concentrations of lithium and LPS were determined in vitro on primary rat astrocytes. Furthermore, qPCR was conducted for gene expression analysis of GFAP and IL-6 markers on primary astrocytes cultured 3D into GelMA and GelMA-PGFs hydrogels with and without lithium and in vitro stimulated with LPS for astrocyte reactivity. The results suggest that the combination of bioactive phosphate-based glass fibers and lithium loading into GelMA structures may impact GFAP expression and early IL-6 expression. Furthermore, GelMA-PGFs (Fe) constructs have shown improved performance in modulating glial scarring over GFAP regulation.

Urinary tract dilation classification system for predicting surgical management and urinary tract infection in neonates and young infants: a systematic review and meta-analysis.

BACKGROUND: The urinary tract dilation classification system has recently been developed to ensure a unified approach to describe urinary tract dilation in neonates and young infants. However, the predictive value of this system for surgical intervention or urinary tract infection (UTI) has not yet been evaluated in a meta-analysis. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the utility of a postnatal urinary tract dilation classification system for predicting surgical management or a UTI occurrence. MATERIALS AND METHODS: As the urinary tract dilation classification system was introduced in 2014, we searched Embase and PubMed databases for studies published between January 2014 and December 2022. Original articles that reported surgical interventions or UTI episodes according to postnatal urinary tract dilation grades were included. The pooled odds ratio (OR) was calculated, using either the fixed-effects or random-effects model, given the lower urinary tract dilation grades as the base category. The quality of the included studies was evaluated using the Newcastle-Ottawa scale. RESULTS: Of the 285 articles reviewed, eight (comprising 2,165 children) were included in the analysis. The studies were of medium-to-high quality. Pooled analysis demonstrated that urinary tract dilation P3 (combined OR, 21.41; 95% confidence interval [CI], 15.72-29.17) and urinary tract dilation P2-P3 (combined OR, 65.17; 95% CI, 33.08-128.38) were associated with surgical intervention. The urinary tract dilation P3 (combined OR, 2.11; 95% CI, 1.56-2.85) and urinary tract dilation P2-P3 (combined OR, 3.36; 95% CI, 2.43-4.63) were associated with UTI episodes. CONCLUSION: The postnatal urinary tract dilation classification system is useful for predicting the need for surgical management and UTI episodes in infants with hydronephrosis.