Tissue Deposition Research Articles

Relevance of Anthocyanin Metabolites Generated During Digestion on Bioactivity Attributed to Intact Anthocyanins

Epidemiological and in vitro studies suggest that dietary anthocyanins in their intact form exert beneficial effects on human health. However, the potential contributions of anthocyanin metabolites to these beneficial effects have been underestimated. The objective of this review was to critically analyze the outcomes of studies concerning the formation, identification, cellular transport, and biological actions of anthocyanin metabolites generated during digestion to formulate several premises supporting the idea that these compounds largely contribute to human health. Studies performed using purified or semi-purified anthocyanins under digestion or physiological conditions were prioritized in this review. It was found that the information available about the digestive stability and metabolism of anthocyanins, as well as about their transport and deposition in human tissues has mostly been generated using plant extracts or tissues naturally containing compounds identified as anthocyanin metabolites or compounds that can serve as precursors of compounds identified as anthocyanin metabolites. This has significantly compromised the accurate identification of anthocyanin metabolites. Studies with pure or semi-purified anthocyanins are scarce in this regard. Some analytical procedures have also led to the unreliable identification and quantification of anthocyanin metabolites and, consequently, to the unreliable determination of their contribution to human health. Evidence suggests that anthocyanins are also highly metabolized in the gastrointestinal tract and transported, stored, and biologically active as their intermediary structures and final metabolites.

Modern surgical treatments for lymphedema.

Lymphedema occurs when the lymphatic system is malformed, leaking or is damaged by infection or cancer treatment. Enlarged extremities due to extensive fluid retention and adipose tissue deposition, recurrent cellulitis, and the requirement for hard-to-wear compression garments lead to impaired limb function and decreased quality of life. This narrative review aims to elucidate classification, diagnostic tools, and conservative management strategies leading the path to patient selection for microsurgical reconstructive procedures or volume reduction procedures. The surgical approaches include reconstructive procedures such as lymphaticovenous anastomosis (LVA) and lymph node transfer and reductive procedures, mainly liposuction and occasionally excisional surgery. Comparing the efficacy of lymphedema surgeries is fully dependent on standardized and reproducible outcome measures. A growing body of knowledge has evolved pointing to the benefits of reconstructive microsurgery of the lymphatic system with or without surgical volume reduction. Tissue engineering and stem cell research leads the way for new approaches. However, several questions remain emphasizing the research needs. Ongoing multicentre trials aiming to elucidate the efficacy and accessibility of surgical treatments for this condition are on their way.

BMP-4 and fetuin A in systemic sclerosis patients with or without calcinosis.

Systemic sclerosis (SSc) is a connective tissue disease at the interface between inflammation and autoimmunity progressively leading to diffuse microvascular and fibrotic involvement of the skin and of multiple internal organs. Approximately, 20-40% of SSc patients suffer from cutaneous calcinosis, a debilitating manifestation due to calcium salt deposition in soft connective tissues, causing pain, ulceration, infection, and deformities, responsible of severe functional limitations. Pathomechanisms are poorly understood as well as markers/molecules capable to predict the risk of patients to develop calcinosis. An observational study was performed in 51 female patients, 25 with and 26 without calcinosis to compare clinical and laboratory parameters and to evaluate pro- and anti-calcifying circulating markers and the in vitro serum calcification potential (T50). Moreover, calcinosis samples were analyzed to characterize their mineral composition. Data demonstrate statistically significant differences in the prevalence of clinical manifestations and ACA and Scl70 autoantibodies in SSc patient with calcinosis compared to those without calcinosis. In SSc patients with calcinosis, serum levels of BMP-4 are higher, fetuin A might be regarded as a potential circulating prognostic marker and a negative correlation was observed between T50 and the global score of clinical manifestations, suggesting a potential predictive role of pro- and anti-calcifying molecules in SSc patients. Furthermore, calcinosis samples were characterized by the co-existence of phosphate and carbonate minerals with different stability and solubility. Further investigations on circulating markers in larger patient cohorts, especially at the early stages and throughout the natural course of the disease, may clarify their pathogenetic role in the SSc-related cutaneous calcinosis.

CLINICAL PROFILE AND MANAGEMENT OF HYPERTROPHIC SCARS AT DR. SOETOMO GENERAL ACADEMIC HOSPITAL SURABAYA, INDONESIA

Highlights: Most hypertrophic scar patients were aged 17 to 25, mainly female, and the scars were mostly caused by burns on the face and upper extremities. Surgical techniques were the most common treatment, with most scars measuring 1 to 5 cm². Abstract: Introduction: Scars is a prevalent clinical concern that is often more complex than commonly perceived. Hypertrophic and keloid scars results from atypical wound healing responses following trauma, characterized by an excessive deposition of connective tissue. In Indonesia, there are remains a paucity of data on the clinical profile and management of hypertrophic scars. To address this gap, researchers conducted a descriptive study to systematically examine various variables associated with hypertrophic scars, aiming to enhance understanding and inform more effective management strategies. Methods: This research is a retrospective descriptive analysis utilizing secondary data from medical records of patients with hypertrophic scars treated at Dr. Soetomo General Academic Hospital in Surabaya during the 2019 – 2020 period. The data were collected and processed according to key variables, including age, gender, occupation, etiology, anatomical location of the hypertrophic scars, scar size, and therapeutic interventions. Results:The number of patients with hypertrophic scars at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from 2019 to 2020 was 68. Most patients were aged 17 to 25 years. The gender distribution was nearly equal, with 50% male and 50.9% female patients. Among the patients, 12.5% and 43% were students. Burns caused 37.5% and 25% of cases. The most common scar locations were the face (25%) and upper extremities (25%). Most scars measured 1 to 5 cm² (25%). The most common treatment was surgical techniques (80% and 48%). Conclusion: Most hypertrophic scar patients were aged 17 to 25 years, predominantly female, and students. The primary cause of the scars was burns, with the scars most commonly located on the face and upper extremities. The majority of scars measured between 1 and 5 cm², and surgical techniques were the most widely used therapy.

FAP+ gastric cancer mesenchymal stromal cells via paracrining INHBA and remodeling ECM promote tumor progression

Gastric cancer (GC) mesenchymal stromal cells (GCMSCs) are the predominant components of the tumor microenvironment (TME) and play a role in the occurrence, development, and metastasis of tumors. However, GCMSCs exhibit phenotypic and functional heterogeneity. The key population of GCMSCs which are vital to tumor progression remains elusive. The expression of fibroblast activation protein (FAP) in gastric cancer was analyzed and verified using clinical pathology data and single-cell RNA sequencing database of gastric cancer patients. FAP positive GCMSCs (FAP+ GCMSCs) were isolated via flow cytometry and characterized through transcriptomic sequencing. The impact of conditioned medium from FAP+ GCMSCs on gastric cancer cell lines was assessed using Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses. Additionally, immunohistochemistry (IHC) and Masson’s trichrome staining were employed to explore the association between FAP+ GCMSCs and extracellular matrix (ECM) deposition in gastric cancer tissues. Our study demonstrates that FAP is predominantly expressed in the mesenchymal stromal cells within the gastric cancer milieu. FAP+ GCMSCs exhibited enhanced proliferation, migration, contraction, and tumor-promoting capabilities compared to their FAP− counterparts. These cells significantly increased proliferation and migration of gastric cancer cells through the paracrine secretion of Inhibin Subunit Beta A (INHBA) and activation of the SMAD2/3 signaling pathway. Moreover, FAP+ GCMSCs also induced collagen deposition in ECM and then up-regulated invasion and stemness of GC cells. Mechanistically, this process was mediated by the interaction of collagen with Integrin Subunit Beta 1 (ITGB1), triggering the phosphorylation of Focal Adhesion Kinase (FAK) and Yes Associated Transcriptional Regulator (YAP). Our findings reveal that FAP+ GCSMCs enhanced the GC progression via releasing cytokine INHBA and remodeling ECM providing a theoretical basis for further exploration of tumor stromal-targeting therapy of gastric cancer.

A polysaccharide from Glycyrrhiza uralensis attenuates myocardial fibrosis via modulating the MAPK/PI3K/AKT signaling pathway

Myocardial fibrosis (MF) is a key factor endangering public health worldwide. Glycyrrhiza uralensis polysaccharide (GPS) exhibits various biological activities. However, its activity against MF has not been reported. Herein, a neutral polysaccharide (GPS-1-1) was isolated from GPS through column chromatography, its structure was characterized and potential mechanism regarding anti-MF activity was evaluated. Notably, the molecular weight of GPS-1-1 was 14.073 kDa, and the monosaccharides consist of glucose, arabinose and galactose, with a → 4)-α-d-glucopyranose (Glcp)-(1 → and →4,6)-α-D-Glcp-(1 → backbone. Western blotting and immunofluorescence showed that GPS-1-1 inhibited the expression of fibrosis-related proteins, such as Collagen, Vimentin, Fibronectin and α-SMA in TGF-β1-induced fibrosis of cardiac fibroblasts (CFs), and inhibited the expression of TGF-β1-induced CFs migration ability and matrix metalloproteinases (MMP-2 and MMP-9), thus inhibiting the deposition of extracellular matrix in CFs. Additionally, in vivo analysis showed that GPS-1-1 reduced inflammatory cell infiltration and collagen deposition in cardiac tissues of mice with MF, and it inhibited the expression of serum lactate dehydrogenase, creatine kinase, and fibrosis-related factors. Combined transcriptomics, molecular docking and Western blotting analysis showed that platelet-derived growth factor subunit B (PDGFB) was involved in the anti-fibrosis process of GPS-1-1. Furthermore, qRT-PCR and Western blotting showed that GPS-1-1 inhibited the expression of MAPK/PI3K/AKT pathway related proteins, such as ERK, p-ERK, JNK, PI3K and p-PI3K in TGF-β1-induced CFs through PDGFB. Altogether, this study showed that GPS-1-1 inhibits the activation of the MAPK/PI3K/AKT pathway by down-regulating PDGFB expression to exert its anti-MF activity and its potential to be developed as a functional food and drug.

Effectiveness of heat source/sink and Lorentz force constraints in a non-Newtonian peristaltic arterial blood hybrid nanofluid past an overlapping stenotic artery

Recently a considerable amount of attention has been directed towards the technological advancements in the study of arterial stenosis. The deposition of adipose tissues and saturated fatty acids and the abnormal growth of flesh, narrows the arteries, leading to restricted blood flow. This causes cardiovascular diseases like atherosclerosis, atherogenesis, atheroma, etc. Considering this the present research paper develops a Casson fluid model to investigate magnetohydrodynamic peristaltic transport of the passage of blood through slightly stenosed arteries due to the influence of copper (Cu) and alumina (Al2O3) nanoparticles. The problem is formulated using appropriate mathematical models employing non-dimensional parameters and stenosis approximations. The study has its applications in the field of medicine. The outcome of this work is that it helps to handle many heart conditions. The findings of this investigation may have benefits in various academic fields, including pharmaceuticals and other industries. In addition, they are remarkably beneficial in the treatment of numerous cardiovascular diseases.

Mitochondrial and Microtubule Defects in Exfoliation Glaucoma.

Exfoliation Syndrome (XFS) is an age-related systemic condition characterized by large aggregated fibrillar material deposition in the anterior eye tissues. This aggregate formation and deposition on the aqueous humor outflow pathway are significant risk factors for developing Exfoliation Glaucoma (XFG), a secondary open-angle glaucoma. XFG is a complex, multifactorial late-onset disease that shares common features of neurodegenerative diseases, such as altered cellular processes with increased protein aggregation, impaired protein degradation, and oxidative and cellular stress. XFG patients display decreased mitochondrial membrane potential and mitochondrial DNA deletions. Here, using Tenon Capsule Fibroblasts (TFs) from Normal (No Glaucoma) and XFG patients, we found that XFG TFs have impaired mitochondrial bioenergetics and increased reactive oxygen species (ROS) accumulation. These defects are associated with mitochondrial abnormalities as XFG TFs exhibit smaller mitochondria that contain dysmorphic cristae, with an increase in mitochondrial localization to lysosomes and slowed mitophagy flux. Mitochondrial dysfunction in the XFG TFs was associated with an increase in the dynamics of the microtubule cytoskeleton, decreased acetylated tubulin, and increased HDAC6 activity. Treatment of XFG TFs with a mitophagy inducer, Urolithin A, and a mitochondrial biogenesis inducer, NAD + precursor, Nicotinamide Ribose, improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate abnormal mitochondria in XFG TFs and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients.

Bushen Jianpi Tiaoxue Decoction (BJTD) ameliorates oxidative stress and apoptosis induced by uterus ageing through activation of the SIRT1/NRF2 pathway

BackgroundUterus ageing is a crucial factor contributing to decreased fertility in older women and is also implicated in menstrual disorders, endometritis, and adenomyosis. Bushen Jianpi Tiaoxue Decoction (BJTD) is a traditional Chinese medicine formulation used to ameliorate endocrine disorders in the female reproductive system and finds extensive application in ageing-related endometrial diseases. However, the mechanisms underlying its improvement of uterus ageing have not been thoroughly investigated. PurposeTo explore the potential components and mechanisms of BJTD in ameliorating uterus ageing through network pharmacology, in vivo, and in vitro experiments. MethodsMorphological changes were observed using hematoxylin and eosin staining, collagen deposition was assessed using Masson staining, and apoptotic-related molecules were detected using Western blot. After determining the modeling doses, BJTD intervention was administered at two doses, and the expression of oxidative stress and apoptosis-related genes and proteins was measured. The levels of cellular apoptosis were evaluated using the TUNEL assay kit and Annexin V/FITC-PI assay kit. The main components of BJTD were determined by UPLC-MS, and the potential targets and mechanisms of BJTD action were explored using network pharmacology and molecular docking. BJTD-Containing Serum (BJTD-S) was extracted and applied in vitro experiments using human endometrial stroma cells (hESC) to preliminarily identify the pathways affected. ResultsWe demonstrated that modeling with 600 mg/kg/day D-Gal for 5 weeks significantly increased collagen deposition in uterine tissues, particularly in the glands and stroma. Additionally, it significantly elevated the levels of TNF-α and IL-1β and increased the expression of p53 and BAX while decreasing BCL-2 expression. BJTD significantly reduced the increased levels of TNF-α and IL-1β induced by D-Gal, and modulated oxidative stress markers such as SOD, MDA, GSH-Px, and T-AOC. BJTD also inhibited the cascade activation of apoptosis induced by D-Gal, suppressing the expression of cleaved-Caspase 8, cleaved-Caspase 3, and BAX. SIRT1 is a potential target of BJTD action. In vitro experiments showed that BJTD-S significantly improved D-Gal-induced apoptosis in hESC cells, and the expression levels of SIRT1, NRF2, and HO-1 were significantly decreased in D-Gal-induced hESC, and BJTD-S significantly increased their expression. ConclusionBJTD can ameliorate oxidative stress and cell apoptosis levels in D-Gal-induced uterine aging, and its active ingredients can activate the SIRT1/NRF2 pathway to exert its effects. Importantly, our study provides novel insights into the molecular mechanisms by which traditional Chinese medicine influence uterus ageing. By specifically targeting the SIRT1/NRF2 pathway, BJTD presents a unique therapeutic approach that has not been extensively explored in previous studies, marking a significant advancement in the treatment of uterus ageing.

Regenerative endodontic therapy in immature teeth using photobiomodulation and photodynamic therapy; a histomorphological study in canine model

BackgroundRegenerative endodontic therapy (RET) is still coming up short to demonstrate histological evidence for true regeneration with clinically feasible protocol of cell homing in single visit approach.AimThe aim of the present study is to evaluate the regenerative potential of photobiomodulation (PBM) on RET in immature roots when photodynamic therapy (PDT) protocol is implemented for root canal disinfection in canine model.Materials and methodsSeventy-two root canals were recruited, with sixty assigned to experimental groups and twelve to positive and negative controls. Following the induction of pulp necrosis and apical periodontitis, the roots were divided into two experimental groups: Group I received RET followed by PBM (seven sessions with an 808 nm diode laser at 300 mW for 90 s), and Group II received RET without PBM. Follow-ups were conducted at 1, 2, and 3 months (subgroups A, B, and C respectively). Qualitative and quantitative assessment was carried out histologically. All data were statistically analyzed with the Mann-Whitney U test and Bonferroni’s adjustment, as well as Chi square test.ResultsThe newly formed hard tissue highly resembled true dentine where the dentinal tubules looked well organized lined by poly layers palisading pattern of rounded odontoblast-like cells with cytoplasmic processes extending through the predentine layer. GI exhibited statistically significantly higher scores of vital tissue infiltration and hard tissue deposition in subgroups A and B (P ≤ 0.05). The inflammatory cells scores were significantly lower in GI than in GII at all time intervals. However, no significance could be detected regarding apical closure.ConclusionThe disinfection protocol of PDT and subsequent irradiation with low power laser in PBM protocol pose a promising potential for regenerative endodontics in immature teeth.

The Lumbar Artery Perforator Free Flap as an Alternative Option for Breast Reconstruction in Low BMI Patients: Analysis of CT Angiography of Donor Sites Across BMI.

In patients with a low body mass index (BMI), the options for autologous breast reconstruction are limited. With the hypothesis that adipose tissue deposition favors the lumbar region over the abdominal wall, this study sought to investigate the lumbar artery perforator (LAP) flap as an alternative reconstructive option in patients with deficient autologous donor sites consequent to a low BMI. A retrospective cohort analysis was performed, from a prospectively maintained database, of all consecutive deep inferior epigastric artery perforator flap breast reconstructions performed in our unit. A randomized selection of 100 patients with low BMI < 22, normal BMI 22 to 24, and high BMI > 30 was performed. Patient computerized tomography scans were analyzed to measure abdominal wall and lumbar tissue thickness and to define anatomical landmark relations of the LAP. A statistically significant difference was identified between the ratio of lumbar-to-abdominal wall thickness between BMI groups, highlighting preservation of the lumbar thickness in patients with low BMI. The mean distance at which the fourth lumbar perforator entered the subcutaneous tissues was 7.7 cm lateral to the spinous process (range 6.4-9.5 cm), with no significant difference between BMI groups, highlighting this consistent anatomical position. This study confirms a greater lumbar-to-abdominal wall thickness, therefore volume, in low BMI patients, with consistent lumbar perforator anatomy of 6.4 to 9.5 cm lateral to the spinous process. The LAP flap should therefore be strongly considered for autologous breast reconstruction in this patient cohort.

Natural Bioactive Compounds: Emerging Therapies for Hyperuricemia.

Hyperuricemia is a crucial feature of metabolic syndrome, characterized by elevated uric acid that causes urate crystal deposits in joints, kidneys, and subcutaneous tissues, resulting in gout and hyperuricemic nephropathy. The primary causes of uric acid metabolism disorder include overproduction and reduced excretion. The majority of uric acid in human body is derived from the breakdown of purine nucleotides. Overproduction of uric acid can result from increased concentration or activity of xanthine oxidase, the key enzyme responsible for uric acid synthesis. Alterations in the activity of proteins responsible for uric acid reabsorption and excretion can also affect serum uric acid. Many bioactive compounds derived from natural plants have been shown to inhibit xanthine oxidase activity to reduce uric acid production, modulate the activity of transport proteins to promote uric acid excretion, or alleviate oxidative stress and inflammation through various signaling pathways. These properties have garnered significant attention from researchers. In this paper, we first introduce the pathophysiological mechanisms of hyperuricemia, then summarize bioactive compounds with urate-lowering effects, and discuss their potential applications in treating hyperuricemia and its complications.

Molecular basis of photoinduced seasonal energy rheostasis in Japanese quail (Coturnix japonica)

Seasonal rhythms in photoperiod are a predictive cue used by many temperate-zone animals to time cycles of lipid accumulation. The neuroendocrine regulation of seasonal energy homeostasis and rheostasis are widely studied. However, the molecular pathways underlying tissue-specific adaptations remain poorly described. We conducted two experiments to examine long-term rheostatic changes in energy stability using the well-characterized photoperiodic response of the Japanese quail. In experiment 1, we exposed quails to photoperiodic transitions simulating the annual photic cycle and examined the morphology and fat deposition in liver, muscle, and adipose tissue. To identify changes in gene expression and molecular pathways during the vernal transition in lipid accumulation, we conducted transcriptomic analyses of adipose and liver tissues. Experiment 2 assessed whether the changes observed in Experiment 1 reflected constitutive levels or were due to time-of-day sampling. We identified increased expression of transcripts involved in adipocyte growth, such as Cysteine Rich Angiogenic Inducer 61 and Very Low-Density Lipoprotein Receptor, and in obesity-linked disease resistance, such as Insulin-Like Growth Factor Binding Protein 2 and Apolipoprotein D, in anticipation of body mass gain. Under long photoperiods, hepatic transcripts involved in fatty acid (FA) synthesis (FA Synthase, FA Desaturase 2) were down-regulated. Parallel upregulation of hepatic FA Translocase and Pyruvate Dehydrogenase Kinase 4 expression suggests increased FA uptake and inhibition of the pyruvate dehydrogenase complex. Our findings demonstrate tissue-specific biochemical and molecular changes that drive photoperiod-induced adipogenesis. These findings can be used to determine conserved pathways that enable animals to accumulate fat without developing metabolic diseases.

Effect of adipose tissue deposition on insulin resistance in middle-aged and elderly women: Based on QCT and MRI mDIXON-Quant.

To explore the relationship between adipose tissue deposition and triglyceride-glucose (TyG) index, an indicator clinically used to assess insulin resistance (IR), in middle-aged and elderly women using quantitative computed tomography (QCT) and MRI mDIXON-Quant sequence. All participants underwent quantitative computed tomography (QCT) and MRI mDIXON-Quant examination and calculated the TyG index based on the fasting blood glucose and triacylglycerol. Bounded by the median TyG index, all participants were divided into low TyG group and high TyG group. Visceral fat mass (VFM) and subcutaneous fat mass (SFM) were measured on QCT images. Hepatic proton density fat fraction (H-PDFF), pancreatic proton density fat fraction (P-PDFF), and lumbar bone marrow fat fraction (L-BMFF) were measured on MRI mDIXON-Quant images. Adjusting for age and body mass index (BMI), TyG was moderately positively correlated with H-PDFF, and r/P was 0.416/<0.001, TyG index was weakly positively correlated with VFM and P-PDFF, and r/P were 0.385/<0.001 and 0.221/0.030. There was a difference of VFM, H-PDFF, and P-PDFF between low TyG group and high TyG group (P < 0.05). Adjusting for age and BMI, VFM, and H-PDFF were the risk factors of high TyG, and H-PDFF was the independent risk factor of high TyG. VFM and H-PDFF were the risk factors of IR, and H-PDFF was the independent risk factor. Early identification and active treatment of adipose tissue deposition, especially hepatic fat deposition, may reserve and delay the progression of IR and even metabolic syndrome.

Abstract 4115801: Assessing Prevalence of Cardiac Amyloidosis at the Time of Spinal Laminectomy for Spinal Stenosis

Introduction: Cardiac amyloidosis (CA) involves deposition of amyloid fibrils within cardiac myocardium, resulting in heart failure. Recent studies have shown an association between amyloid deposition in the ligamentum flavum (LF) and development of CA. Our study aims to investigate the prevalence of CA in patients identified with amyloid deposition in their LF at the time of spinal laminectomy for spinal stenosis, employing a comprehensive approach integrating multi-modality imaging and laboratory testing. Methods: This is a retrospective study of patients age &gt;50 years old who underwent spinal laminectomy for non-congenital spinal stenosis or spondyloarthropathy. LF tissue samples obtained during surgery were examined histologically for amyloid deposition. Patients with positive findings underwent testing, including serum markers, echocardiography, and 99mtechnetium pyrophosphate (99mTcPYP) scintigraphy. Additionally, cardiac magnetic resonance imaging (cMRI) was obtained when clinically appropriate to assess for CA. Results: Among the 197 enrolled patients, 39 (19.3%) exhibited amyloid deposition in LF tissue. Patient demographics and clinical characteristics did not significantly differ between the positive and negative groups (Table 1). Of the 39 amyloid positive specimens, subtyping using mass spectrometry identified 1 (3%) light-chain, 28 (72%) transthyretin (TTR), and 10 (25%) were unable to be subtyped. Of the 28 TTR positive patients, 8 were of the wild type genotype. Furthermore, 18 of the 28 TTR patients underwent 99mTcPYP scintigraphy, of which none had cardiac uptake consistent with TTR amyloidosis; the other 10 declined work up. Of the 10 untyped patients, 6 had 99mTcPYP scintigraphy with none of the patients having cardiac uptake. Adjunctive cMRI in select positive patients showed findings inconsistent with amyloid deposition. Serum NT-proBNP, Troponin T, and serum pre-albumin levels were similar between groups. Conclusion: Amyloid deposition in LF tissue did not correlate with cardiac manifestations of amyloidosis at the time of surgery. Longitudinal investigation is ongoing to better understand the relationship between amyloid deposition in LF tissue and the development of CA over time.

Ginger Extract Improves Cognitive Dysfunction via Modulation of Gut Microbiota-Derived Short-Chain Fatty Acids in D-Galactose/Ovariectomy-Induced Alzheimer-Like Disease.

Alzheimer's disease (AD) is the most common form of dementia with complex causes and limited treatment options. Recent research has suggested a connection between the progression of AD and the activity of gut microbiota. Ginger, a plant known for its anti-inflammatory, antioxidant, and neuroprotective properties, has gained attention as a potential treatment for alleviating AD symptoms. In this study, we induced an AD model in female rats through ovariectomy and D-galactose injection and then investigated the protective effects of oral administration of ginger ethanolic extract. We assessed changes in short-chain fatty acids (SCFAs), learning and memory abilities, neuroinflammatory markers in plasma, and the hippocampus, as well as histological changes in the intestine and hippocampus in sham-operated, diseased, and treatment groups. Oral administration of ginger ethanolic extract improved gut microbiota activity, increased SCFA levels, and enhanced the expression of tight junction proteins. Additionally, ginger extract reduced the concentrations of TNF-α and IL-1β in both plasma and the hippocampus. Furthermore, it significantly reduced cell death and amyloid plaque deposition in the hippocampal tissue. These physiological changes resulted in improved performance in learning and memory tasks in rats treated with ginger compared with the disease group. These findings provide compelling evidence for the beneficial effects of ginger on the gut-brain axis, leading to improvements in learning and memory through the reduction of neuroinflammation.

Efficacy and Safety of Daratumumab in Light Chain Amyloidosis: A Single-Center Retrospective Study

Purpose Light chain amyloidosis (AL) is a disease marked by the misfolding of immunoglobulin light chains, leading to amyloid deposits in various tissues and organs. The prognosis is particularly poor for patients with significant organ involvement. Daratumumab, an anti-CD38 monoclonal antibody, has shown promising results with an overall response rate (ORR) exceeding 80% in various studies. This retrospective study aims to evaluate the efficacy and safety of Daratumumab in treating AL amyloidosis, providing additional clinical insights. Methods The study included newly diagnosed or relapsed/refractory AL patients treated at Tongji Hospital, Huazhong University of Science and Technology, between May 2021 and May 2024. Patients received at least three courses of Daratumumab, administered in various regimens: Daratumumab with lenalidomide and dexamethasone (DRD group), bortezomib and dexamethasone (DVD group), pomalidomide and dexamethasone (DPD group), selinexol and dexamethasone (SDD group), isazomib and dexamethasone (DID group), dexamethasone alone (DD group), and carfizomib and dexamethasone (DKD group). Efficacy was measured through hematological remission and organ response. Results The study cohort consisted of 41 patients, with 31 initially diagnosed and 10 relapsed/refractory. The median age was 59 years (range: 38-75). Of these patients, 56.1% were classified as Mayo stage III-IV, with 76% having cardiac involvement, 52% with renal involvement, and 13 with dual cardiac and renal involvement. Median NT-proBNP was 2375 ng/L, median 24-hour urine protein was 0.683 g, median estimated glomerular filtration rate (eGFR) was 71.1 mL/min/1.73 m², and median difference free light chain (dFLC) was 132.05 mg/L. The DRD group showed 72.2% achieving very good partial response (VGPR) or better at 12 months, while 60% in the DVD group reached similar outcomes. Overall, the ORR at one month was 53.6% (22/41), including 4 complete remissions (CR), 14 VGPR, and 4 partial remissions (PR). At six months, the ORR increased to 72.9% (27/37), with 10 CRs, 13 VGPRs, and 4 PRs, reaching 90.9% (10/11) at 12 months, comprising 8 CR, 1 VGPR, and 1 PR. Cardiac response rates improved from 48.3% at three months to 78% at six months and 85% at 12 months. Among those with renal involvement, 52.3% demonstrated an organ response at 12 months. These findings indicate that Daratumumab not only significantly improves hematological outcomes but also promotes recovery of organ function. Conclusion This retrospective study confirms that Daratumumab is an effective and safe treatment option for AL amyloidosis, delivering rapid and sustained hematologic and organ responses. Most adverse events were mild and manageable, affirming the treatment's safety profile. However, the retrospective design and small sample size may limit the study's applicability. Larger, randomized controlled trials are necessary to validate these findings and further optimize the use of Daratumumab in clinical practice for AL amyloidosis.

4‑Methoxydalbergione inhibits the tumorigenesis and metastasis of lung cancer through promoting ferroptosis via the DNMT1/system Xc‑/GPX4 pathway.

Lung cancer is responsible for the highest number of tumor‑related deaths worldwide. A flavonoid extracted from the heartwood of Dalbergia sissoo Roxb., 4‑methoxydalbergione (4‑MD), exhibits potent anticancer activity in multiple malignancies; however, the potential anticancer activity of 4‑MD in lung cancer has not yet been elucidated. In the present study, A549 cells were treated with increasing concentrations of 4‑MD, and cell viability was assessed using a Cell Counting Kit‑8 assay. In addition, colony formation, 5‑ethynyl‑2'‑deoxyuridine, wound healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Cell morphology was observed using transmission electron microscopy, and ferroptosis was determined using thiobarbituric acid reactive substance, lipid reactive oxygen species (ROS) and iron assays. Moreover, molecular docking was used to verify the potential interaction between 4‑MD and DNA methyltransferase 1 (DNMT1). Tumor‑bearing mice were established and treated with 10 or 30 mg/kg 4‑MD, and tumor volume and weight were recorded. Immunohistochemistry and Prussian blue staining were conducted to examine Ki‑67 expression and iron deposition in tumor tissues, and protein expression was further explored using western blot analysis. The results of the present study revealed that 4‑MD significantly inhibited cell proliferation, migration, invasion and epithelial‑mesenchymal transition in a concentration‑dependent manner. Notably, 4‑MD induced ferroptosis via increased lipid peroxidation, lipid ROS and Fe2+ levels. In addition, it was revealed that 4‑MD can directly bind to DNMT1 to inhibit expression, and inhibit solute carrier family 7 member 11 (SLC7A11; also known as cystine‑glutamate antiporter) and glutathione peroxidase 4 expression. Following DNMT1 overexpression, the observed antitumor activity and ferroptosis‑promoting effects of 4‑MD were partially reversed. Furthermore, 4‑MD significantly inhibited tumor growth in vivo, and reduced tumor volume and weight. In addition, Ki‑67 expression was reduced while iron deposition was increased in the tumor tissues of mice following treatment with 4‑MD. In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.

Euglena Attenuates High-Fat-Diet-Induced Obesity and Especially Glucose Intolerance.

Background: Obesity, a global disease, can lead to different chronic diseases and a series of social health problems. Lifestyle changes, especially dietary changes, are the most effective way to treat obesity. Euglena, a novel food, has attracted much attention. Previous studies have shown that Euglena is an important modulator of the host immune response. In this study, the effects of Euglena as a nutritional intervention in high-fat-diet-induced obese C57BL/6J mice were investigated regarding adipose tissue accumulation and lipid and glucose metabolism by gavage at the dose of 100 mg/kg bodyweight for 9 weeks. This study is one of the few to investigate, in detail, the preventive effects of dietary Euglena on obesity. Methods: Five-week-old male C57BL/6J mice were fed with a high-fat diet (HFD) to induce obesity. An obesity model was created by feeding the high-fat diet for a period of 10 weeks. Obese mice were randomized into 2 groups with the same mean body weight, and no significant differences were observed between the groups: (1) the mice in the HEG group were maintained on a high-fat diet and daily gavaged with Euglena (100 mg/kg body weight) dissolved in saline (n = 7); and (2) the mice in the HFD group were maintained on a high-fat diet and daily gavaged with saline with the same volume (n = 7). The experiment finished after a nine-week period. Results: The results showed that Euglena could reduce the accumulation of white body fat, including subcutaneous fat and visceral fat, and mainly targeted subcutaneous fat. Euglena also reduced adipocyte particle size expansion, promoted lipolysis in adipose (adipose triglyceride lipase and hormone-sensitive triglyceride lipase) and liver tissue (reduced non-esterified fatty acid content), and improved obesity-induced ectopic fat deposition and glucose tolerance. Conclusions: Our findings suggest that Euglena, as a nutritional intervention in HFDs, efficiently reduces body weight and white adipose tissue deposition. The mechanism of Euglena is mainly though enhancing lipolysis. It is worth noting that Euglena β-glucan recovers the hyperglycemia and accumulation of ectopic fat within the liver induced by HFD. Our study is one of the few studies to report in detail the preventive effects of dietary Euglena on obesity in vivo. This study revealed that Euglena also has an important ameliorative effect on obesity and metabolic disorders, which laid a theoretical foundation for its future application in functional foods.

Targeted CRISPR regulation of ZNF865 enhances stem cell cartilage deposition, tissue maturation rates, and mechanical properties in engineered intervertebral discs

Cell and tissue engineering based approaches have garnered significant interest for treating intervertebral disc degeneration and associated low back pain due to the substantial limitations of currently available clinical treatments. Herein we present a clustered regularly interspaced short palindromic repeats (CRISPR)-guided gene modulation strategy to improve the therapeutic potential of cell and tissue engineering therapies for treating intervertebral disc disease. Recently, we discovered a zinc finger (ZNF) protein, ZNF865 (BLST), which is associated with no in-depth publications and has not been functionally characterized. Utilizing CRISPR-guided gene modulation, we show that ZNF865 regulates cell cycle progression and protein processing. As a result, regulating this gene acts as a primary titratable regulator of cell activity. We also demonstrate that targeted ZNF865 regulation can enhance protein production and fibrocartilage-like matrix deposition in human adipose-derived stem cells (hASCs). Furthermore, we demonstrate CRISPR-engineered hASCs ability to increase GAG and collagen II matrix deposition in human-size tissue-engineered discs by 8.5-fold and 88.6-fold, respectively, while not increasing collagen X expression compared to naive hASCs dosed with growth factors. With this increased tissue deposition, we observe significant improvements in compressive mechanical properties, generating a stiffer and more robust tissue. Overall, we present novel biology on ZNF865 and display the power of CRISPR-cell engineering to enhance strategies treating musculoskeletal disease. Statement of significanceThis work reports on a novel gene, ZNF865 (also known as BLST), that when regulated with CRISPRa, improves cartilagenous tissue deposition in human sized tissue engineering constructs. Producing tissue engineering constructs at human scale has proven difficult, and this strategy presents a broadly applicable tool to enhance a cells ability to produce tissue at these scales, as we saw an ∼8–88 fold increase in tissue deposition and significantly improved biomechanics in large tissue engineered intervertebral disc compared to traditional growth factor differentiation methods. Additionally, this work begins to elucidate the biology of this novel zinc finger protein, which appears to be critical in regulating cell function and activity.