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Background: The impact of a high-salt (HS) diet on metabolic disturbances in individuals with coronary heart disease remains unclear. The arachidonic acid (AA) metabolic pathway is closely linked to the development of cardiometabolic diseases and atherosclerotic cardiovascular diseases. Furthermore, endoplasmic reticulum stress (ERS) has emerged as a major contributor to cardiometabolic diseases. AA-related inflammation and ERS are hypothesized to play a role in HS diet-induced coronary remodeling. Methods: Rats were subjected to an HS diet for 4 weeks, and the serum concentration of AA was measured via enzyme-linked immunosorbent assay. Immunofluorescence staining and vascular tension measurements were conducted on coronary arteries. In addition, AA-stimulated coronary artery smooth muscle cells (CASMCs) were treated with ERS inhibitors to explore the underlying pathway involved. Results: Increased susceptibility to myocardial infarction in the HS diet-fed rats was accompanied by increased serum AA concentrations and increased expression of the key AA metabolic enzyme cyclooxygenase-2 (COX-2). AA incubation weakened the contraction of denuded coronary arteries, reduced the expression of contraction markers, and increased the fluorescence intensity of synthetic and ERS response markers in coronary arteries. Further investigation of CASMCs revealed that AA-induced phenotypic transformation was mediated via the ERS pathway. Conclusions: ERS and AA were found to be stimulated in CASMCs following an HS diet. AA triggers an ERS response through COX-2 catalysis, and the downstream inositol requiring enzyme 1 - X-box binding protein-1 - osteopontin pathway may contribute to the AA-induced phenotypic transformation of CASMCs, resulting in dysfunctional coronary tension. This study may provide potential therapeutic targets for cardiovascular diseases associated with excessive AA-derived ERS. [ABSTRACT FROM AUTHOR]

Clinical studies of the urinary tract microbiome, termed urobiome, suggest a direct, antibiotic-dependent, impact of the urobiome on kidney physiology. However, evidence for kidney bacteria comes from indirect sources or infected tissue. Further, it is unclear how antibiotics impact kidney bacteria. Here we show direct evidence for the presence of bacteria in the kidneys, with microniches in nephrons. In murine kidneys, administration of cefazolin, a commonly used perioperative antibiotic, led to a loss of uroprotective Lactobacillus spp. and proliferation of Enterobacteriaceae (which includes many known uropathogens). This effect was dependent on treatment duration, with recovery post treatment. Uroprotective L. crispatus and a strain of stone-associated E. coli differentially influenced calcium oxalate (CaOx) crystallization through the incorporation of CaOx inhibitors or promoters, respectively. In humans, microbial signatures were identified in the kidney, with unique niches between the glomeruli and tubules, established through RNA sequencing analysis and direct imaging of two independent populations. Collectively, findings support the hypothesis that the kidneys harbor a stable and antibiotic-responsive microbiota that can influence CaOx lithogenesis. The presence of unique, age-dependent microbial signatures in the glomeruli and tubuli carry implications for non-infectious kidney diseases. Here, the authors provide evidence that the renal microbiome can be disrupted by antibiotics, leading to differential effects on anti-lithogenic taxa like Lactobacillus and pro-lithogenic bacteria such as Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and Objectives: The incidence of kidney stones is increasing globally, with a preponderance in adults compared with that in adolescents and children. Dietary habits have been identified as significant contributing factors to kidney stone formation. This literature review aimed to explore the existing evidence on the impact of diet on renal stone formation. Methods and Study Design: We conducted a comprehensive literature review and included 81 studies published between 1999 and 2023, limiting the search to articles published in English. The extracted data were analyzed to identify common themes, trends, and patterns related to the impact of diet on renal stone formation. We investigated the influence of dietary habits on the risk of nephrolithiasis. Results: Although the role of fluid intake in relation to stone formation is clear, existing evidence on how different types of beverages (coffee, tea, fruit juices, and soft drinks) affect kidney stone formation is conflicting. Other factors such as protein, sodium chloride, calcium, oxalate, fat, and carbohydrate intake have also been discussed as contributors to nephrolithiasis. Thus, diet should be appropriately modified to reduce the risk of stone formation in susceptible individuals. A history of nephrolithiasis has been found to increase the risk of both chronic kidney disease and end-stage renal disease. The review acknowledges the limitations inherent in conducting a literature review, including the potential for publication bias and the reliance on available published studies. Conclusions: These findings highlight the importance of understanding and preventing nephrolithiasis. [ABSTRACT FROM AUTHOR]

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Context: Polygenic urolithiasis has a complicated etiology and even more varied therapeutic outcomes. Spermacoce articularis L.f. has been used historically for stone treatments in several traditional medical systems. Aim: The current study aimed to investigate the in vitro and in vivo anti-urolithiatic potential of Spermacoce articularis Stem Extract (SASE). Methods: In vitro antiurolithiatic potential on the CaOx crystallization was evaluated using nucleation and aggregation assays. In vivo, activity was assessed on renal calculi-induced Wistar rats by polyethylene glycol (0.75%) in drinking water for 14 days. SASE and cystone with two experimental doses (250 and 500 mg/kg, p.o.) were dispensed for ten days. Various biochemical parameters were assessed in the kidneys' serum, urine, and histological sections. In addition, SASE inhibited CaOx crystallization by reducing the density of crystals, triggering the breakdown of CaOx crystals, and hindering their growth. Cystone demonstrated comparable outcomes. Results: Upon treatment with SASE, urinary, serum, kidney homogenates, and antioxidants were significantly improved (p<0.05) to normal levels. The histopathology of the kidney section showed no damaged cells of SASE treated and Cystone treated compared with that of control animals. Conclusion: This research validates the traditional idea and suggests that SASE is advantageous in preventing the growth of urinary stones. [ABSTRACT FROM AUTHOR]

Despite the apparent importance of matrix proteins in calcium oxalate kidney stone formation, the complexity of the protein mixture continues to elude explanation. Based on a series of experiments, we have proposed a model where protein aggregates formed from a mixture containing both strongly charged polyanions and strongly charged polycations could initiate calcium oxalate crystal formation and crystal aggregation to create a stone. These protein aggregates also preferentially adsorb many weakly charged proteins from the urine to create a complex protein mixture that mimics the protein distributions observed in patient samples. To verify essential details of this model and identify an explanation for phase selectivity observed in weakly charged proteins, we have examined primary structures of major proteins preferring either the matrix phase or the urine phase for their contents of aspartate, glutamate, lysine and arginine; amino acids that would represent fixed charges at normal urine pH of 6–7. We verified enrichment in stone matrix of proteins with a large number of charged residues exhibiting extreme isoelectric points, both low (pI<5) and high (pI>9). We found that the many proteins with intermediate isoelectric points exhibiting preference for stone matrix contained a smaller number of charge residues, though still more total charges than the intermediate isoelectric point proteins preferring the urine phase. While other sources of charge have yet to be considered, protein preference for stone matrix appears to correlate with high total charge content. [ABSTRACT FROM AUTHOR]

Disruption-generated runaway electron (RE) beams represent a potentially severe threat for tokamak plasma-facing components. Application of properly designed 3D fields can act as a mitigation mechanism, as recently investigated in ASDEX Upgrade (AUG) and COMPASS experiments and in the tokamak discharges of RFX-mod. In all of these devices, the dynamics of the disruption are affected by the application of magnetic perturbations (MPs), and the resulting RE beam current and lifetime are significantly reduced. These experiments show, in particular, that the strength of the observed effects strongly depends on the poloidal spectrum of the applied MPs, which has been reconstructed including the plasma response. This paper reports the main findings on RE mitigation from the previously mentioned three devices, highlighting the common physics behind them and their interpretation by using the guiding center code ORBIT. [ABSTRACT FROM AUTHOR]

Aim: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up: Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. Prophylaxis: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. Future research: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation. [ABSTRACT FROM AUTHOR]

An aborted female foal was submitted for necropsy. During the gross examination, the ovaries were pale, grayish, and enlarged (6 × 5cm), with a well-developed vascular structure surrounding the external surface; the cut surface of the ovaries showed a brownish parenchyma with white follicular areas mainly localized in the peripheral region. The ovaries were fixed for histological investigations. The histological evaluation of the ovaries showed polygonal-shaped cells with abundant cytoplasm and round or oval nuclei, arranged in cords of single cells. The tissue architecture was characterized by the presence of lobular-like tissues with a central vein. The tissue mimicking hepatocytes was delimited by a mature fibrous tissue and was surrounded by the normal ovarian tissue characterized by germinal epithelium and primordial follicular structures. Based on the histological findings, a diagnosis of bilateral ovarian hamartoma was carried out initially. For a better characterization of the ovarian tissue, the expression of tissue-specific (liver and ovary) markers was investigated using immunohistochemistry. Following the immunohistochemical analysis, the hamartoma diagnosis was excluded. The ovaries exhibited unique characteristics different from those of adult horse ovaries as well as unique morphological features different fromothermammalian species. This case report enhances our understanding of ovaries at a later stage of pregnancy and unveils unique characteristics of horse ovaries development, avoidingmisdiagnosis with pathological findings, hamartomas, or neoplasia. [ABSTRACT FROM AUTHOR]

Background: Dental pulp calcifications or pulp stones are calcified structures found in dental pulp, mostly around or enclosing a blood vessel. The formation of these calcifications begins with concentric layers of calcified tissue within which remnants of necrotic and calcified cells may be present. The calcifications of thrombi in blood vessels, called phleboliths, may also serve as nidi for denticles. In metabolic diseases such as diabetes, hypertension or poor periodontal health, there are obvious changes in blood vessels and vascularization. In our study, we observed histopathological sections of dental pulp and correlated systemic diseases such as diabetes and hypertension with poor periodontal health and dental pulp stones. Aim: The aim of our study was to evaluate the histopathology of dental pulp stones, their distribution among various age groups and sexes and to identify any correlations between pulp stone formation and systemic diseases such as type II diabetes and hypertension. Materials and Methods: Samples from 100 patients with metabolic diseases such as type II diabetes and hypertension were collected. The pulp was extirpated from the teeth that were undergoing root canal treatment, and the teeth were extracted. The collected pulp sample was fixed in 10% formaline neutral buffer, subjected to routine histopathological procedures and stained with haematoxylin and eosin. The pulp of teeth extracted for orthodontic treatment was considered a control for patients with no metabolic disease. Results: There was a definite relationship between increased pulp stones and metabolic diseases such as type II diabetes and hypertension; likewise, poor periodontal health was significantly related to pulp stones. [ABSTRACT FROM AUTHOR]

Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi‐step and long‐term process involving the transformation of stone‐forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic lung disease characterized by abnormal proliferation and activation of fibroblasts, excessive accumulation of extracellular matrix (ECM), inflammatory damage, and disrupted alveolar structure. Despite its increasing morbidity and mortality rates, effective clinical treatments for IPF remain elusive. Osteopontin (OPN), a multifunctional ECM protein found in various tissues, has been implicated in numerous biological processes such as bone remodeling, innate immunity, acute and chronic inflammation, and cancer. Recent studies have highlighted the pivotal role of OPN in the pathogenesis of IPF. This review aims to delve into the involvement of OPN in the inflammatory response, ECM deposition, and epithelial-mesenchymal transition (EMT) during IPF, and intends to lay a solid theoretical groundwork for the development of therapeutic strategies for IPF. [ABSTRACT FROM AUTHOR]

The neutrophils exhibit both anti-tumor and pro-tumor effects in cancers. The correlation between neutrophils and tumor development in lung adenocarcinoma (LUAD) is still uncertain, possibly due to a lack of specific neutrophil infiltration evaluation methods. In this study, we identified 30 hub genes that were significantly associated with neutrophil infiltration in LUAD through data mining, survival analysis, and multiple tumor-infiltrating immune cells (TICs) analysis, including TIMER, CIBERSORT, QUANTISEQ, XCELL, and MCPCOUNTER. Consensus clustering analysis showed that these 30 hub genes were correlated with clinical features in LUAD. We further developed a neutrophil scoring system based on these hub genes. The neutrophil score was significantly correlated with prognosis and tumor immune microenvironment (TIME) in LUAD. It was also positively associated with PD-L1 expression and negatively associated with tumor mutational burden (TMB). When combined with the neutrophil score, the predictive capacity of PD-L1 and TMB for prognosis was significantly improved. Thus, the 30 hub genes might play an essential role in the interaction of neutrophils and LUAD, and the neutrophil scoring system might effectually assess the infiltration of neutrophils. Furthermore, we verified the expression of these 30 genes in the LUAD tumor tissues collected from our department. We further found that overexpressed TNFAIP6 and TLR6 and downregulated P2RY13, SCARF1, DPEP2, PRAM1, CYP27A1, CFP, GPX3, and NCF1 in LUAD tissue might be potentially associated with neutrophils pro-tumor effects. The following in vitro experiments demonstrated that TNFAIP6 and TLR6 were significantly overexpressed, and P2RY13 and CYP27A1 were significantly downregulated in LUAD cell lines, compared to BEAS-2B cells. Knocking down TNFAIP6 in A549 and PC9 resulted in the upregulation of FAS, CCL3, and ICAM-1, and the downregulation of CCL2, CXCR4, and VEGF-A in neutrophils when coculturing with the conditioned medium (CM) from LUAD cells. Knocking down TNFAIP6 in LUAD also led to an elevated early apoptosis rate of neutrophils. Therefore, overexpressed TNFAIP6 in LUAD cancer cells might lead to neutrophils "N2" polarization, which exhibited pro-tumor effects. Further research based on the genes identified in this pilot study might shed light on neutrophils' effects on LUAD in the future. [ABSTRACT FROM AUTHOR]

Background/Aim: As one of the common clinical diseases, fractures have many causes, mechanisms, healing and influencing factors; especially fracture healing is a longterm and complex process. Animal fracture models can simulate the various states of human fractures, and on this basis, the prevention, mechanism, and treatment of fractures can be studied to further guide clinical practice. Materials and Methods: Here, we developed a novel and portable device to create a closed fracture model in mice. We then compared this novel closed fracture model with the traditional open model in multiple dimensions to evaluate the modelling process of establishment and healing. The two models were evaluated by imaging, immunostaining, and behavioral tests, which fully demonstrated the stability, universality and operability of the modified fracture model in mice. Results: Surgical quality assessment revealed that the closed fracture model had a shorter operation time and smaller wound than the open model. X-ray and micro-CT results showed no differences between the two models in the evaluation of radiographic and morphological changes during fracture healing. Histological examination revealed the process of the typical intrachondral osteogenic pathway after fracture. Moreover, animal gait analysis indicated reduced postoperative pain in the closed group compared to the open group. Conclusion: This study provides a constructive strategy for a closed fracture model in mice and demonstrates the effectiveness and feasibility of the closed fracture model in studying the typical intrachondral osteogenic pathway of fractures from multiple dimensions. [ABSTRACT FROM AUTHOR]

Oysters have unique life history strategies among molluscs and a long history in the fossil record. The Ostreid form, particularly species from the genus Crassostrea , facilitated the invasion into intertidal, estuarine habitats and reef formation. While there is general acknowledgement that oysters have highly variable growth, few studies have quantified variability in oyster allometry. This project aimed to (1) describe the proportional carbonate contributions from each valve and (2) examine length–weight relationships for shell and tissue across an estuarine gradient. We collected 1122 C. virginica from 48 reefs in eight tributaries and the main stem of the Virginia portion of the Chesapeake Bay. On average, the left valve was responsible for 56% of the total weight of the shell, which was relatively consistent across a size range (24.9–172 mm). Nonlinear mixed-effects models for oyster length–weight relationships suggest oysters exhibit allometric growth (b < 3) and substantial inter-reef variation, where upriver reefs in some tributaries appear to produce less shell and tissue biomass on average for a given size. We posit this variability may be due to differences in local conditions, particularly salinity, turbidity, and reef density. Allometric growth maximizes shell production and surface area for oyster settlement, both of which contribute to maintaining the underlying reef structure. Rapid growth and intraspecific plasticity in shell morphology enabled oysters to invade and establish reefs as estuaries moved in concert with changes in sea level over evolutionary time. [ABSTRACT FROM AUTHOR]

The study aimed to explore the effect of the nuclear factor-kappa B signaling pathway on apoptosis of rat renal tubular epithelial cells caused by calcium oxalate monohydrate crystals. After being cultivated in vitro, NRK-52E cells were split into a control group, 1 mm calcium oxalate monohydrate group and 10 μM QNZ+1 mm calcium oxalate monohydrate group. The optical density value was detected via cell counting kit-8 assay, the content of lactate dehydrogenase in cell supernatant was detected via colorimetry, and the expressions of nuclear factor-kappa B signaling pathway-related proteins p65 and p50 and B cell lymphoma-2, tumor necrosis factor receptor 1 and caspase-3 were determined through Western blotting. 1 mm calcium oxalate monohydrate could significantly reduce the proliferation ability of NRK-52E cell and cause cytotoxicity. 1 mm calcium oxalate monohydrate significantly up-regulated the expressions of p65, p50, tumor necrosis factor receptor 1 and caspase-3, and significantly lowered the B cell lymphoma-2. Besides, 10 μM QNZ+1 mm calcium oxalate monohydrate obviously down-regulated the expressions of p65, p50, tumor necrosis factor receptor 1 and caspase-3, and obviously increased the B cell lymphoma. The apoptosis of rat renal tubular epithelial cells in rats with calcium oxalate kidney stones may be promoted through activating the nuclear factor-kappa B signaling pathway. Inhibiting the nuclear factor-kappa B activity can alleviate apoptosis and improve renal cell function. [ABSTRACT FROM AUTHOR]

Introduction: Urolithiasis is one of the most prevalent diseases worldwide. Its prevalence is rising, both in developing and developed countries. It is known that genetic factors play big roles in the development of urolithiasis. One of the suspected factors is gene polymorphism. This study aims to find an accurate estimate of the association between genetic polymorphism and the risk of recurrent urolithiasis. Methods: A systematic review and meta-analysis were performed on 12 studies from 3 databases that investigated gene polymorphism as an risk factor of urolithiasis. The review was done using Review Manager® version 5.3. Results: Insignificant heterogenicity was found in this study. Populations from Asia and the Middle East are more likely to experience recurrent urolithiasis. Additionally, variation in the VDR and urokinase genes, particularly in the Asian population, increases the risk of developing recurrent urolithiasis. Conclusions: Gene polymorphisms have significant roles in the development of urolithiasis, especially in the Middle Eastern region. [ABSTRACT FROM AUTHOR]

The crude extract of Trachyspermum ammi seeds (Ta.Cr) was studied for its antiurolithic activity using the in vivo and in vitro experiments. In the in vivo experiments, Ta.Cr treatment showed a diuretic activity at the dose of 30 and 100 mg/kg and exhibited curative effect in male hyperoxaluric Wistar rats, which received 0.75% ethylene glycol (EG) in drinking water given for 3 weeks, with 1% ammonium chloride (AC) for initial three days. In the in vitro experiments, Ta.Cr delayed the slopes of nucleation and inhibited the calcium oxalate (CaOx) crystal aggregation in a concentration-dependent manner like that of potassium citrate. Ta.Cr also inhibited DPPH free radicals like standard antioxidant drug butylated hydroxytoluene (BHT), and significantly reduced cell toxicity and LDH release in Madin–Darby canine kidney (MDCK) cells, exposed to oxalate (0.5 mM) and COM (66 µg/cm2) crystals. In isolated rabbit urinary bladder strips, Ta.Cr relaxed high K+ (80 mM) and CCh (1 µM)-induced contractions, showing antispasmodic activity. The findings of this study suggest that the antiurolithic activity of crude extract of Trachyspermum ammi seeds may be mediated by a number of mechanisms, including a diuretic, an inhibitor of CaOx crystal aggregation, an antioxidant, renal epithelial cell protection, and an antispasmodic, thus, showing the therapeutic potential in urolithiasis, for which there is no viable non-invasive option in modern medicine. [ABSTRACT FROM AUTHOR]

Melon seed extracts have high antioxidant activities and are effective against a variety of diseases, including kidney stones. In kidney stone model rats, the anti-urolithiatic effects of the hydro-ethanolic extract of melon seed and potassium citrate were studied and compared. After urolithiasis induction by ethylene glycol, the extract and potassium citrate were treated orally for 38 days concurrent with ethylene glycol. Then, urine and kidney sampling were done, and the urinary parameter levels were measured. The melon and potassium citrate treatments reduced the kidney index, the levels of urinary calcium and oxalate, calcium oxalate deposit numbers, the score of crystal deposits, histo-pathological damages, and the score of inflammation in the kidney sections, while elevating the urinary pH, magnesium, and citrate levels, and also the expression of the UMOD, spp1, and reg1 genes in the kidney of treated animals. The effect of potassium citrate is the same as the effect of melon in treated animals. So, their effects could be by normalizing urinary parameters, reducing crystal deposits, excreting small deposits from the kidney, reducing the chance of them being retained in the urinary tract, and elevating the expression of the UMOD, spp1, and reg1 genes, which are involved in kidney stone formation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Nephrolithiasis is a common cause of kidney insufficiency. Nephrolithiasis is proven to be the result of various biochemical and inflammatory processes that result in crystal formation and subsequent aggregation. Cotinus coggygria L. (CCog) is a plant extract which has been used as a Turkish remedy for kidney stones. With this study, we planned to evaluate the effects of CCog extract in ethylene glycol (EG)-induced nephrolithiasis model in rats. METHODS: The study group comprised 32 Wistar albino rats which were divided into Control (C), EG, CCog Prophylaxis (CC+EG+CC), and CCog Treatment (EG+CC) groups. Stone formation was induced by adding EG (0.75%) into rat's drinking water. Normal drinking water was given to Control group for 8 weeks. Throughout the study period of 8 weeks, EG group was given only EG (0.75%) and CC+EG+CC group was given both EG and CCog. In EG+CC group, EG (0.75%) was given for 8 weeks whereas CCog was given for the past 4 weeks. After the 8th week, 24-h urine samples were collected. Rats were then sacrificed and kidney tissue samples were harvested. RESULTS: Metabolites (calcium, citrate) and creatinine in 24 h urine samples were decreased in CC+EG+CC and EG+CC groups. While hyperoxaluria was observed in the EG group, oxalate levels were similar to control levels in the P-CCog and C-CCog groups. The N-acetyl-ß-glucosaminidase and myeloperoxidase activities were both increased in EG group and these parameters were significantly decreased on CCog treatment. CONCLUSION: We can conclude that C. coggygria extract can have beneficial effect on lowering concentration of stone-forming metabolites in urine and consequently protect renal tissues from damage due to nephrolithiasis. C. coggygria extract can be considered as a potential prophylactic and therapeutic option in high-risk stone formers. Furthermore, our data confirm ethnobotanical use of CC against nephrolithiasis. [ABSTRACT FROM AUTHOR]

Introduction: Graves' disease is an autoimmune disorder caused by autoantibodies against the thyroid stimulating hormone receptor (TSHR). Overstimulation of the TSHR induces hyperthyroidism and thyroid eye disease (TED) as the most common extra thyroidal manifestation of Graves' disease. In TED, the TSHR cross talks with the insulin-like growth factor 1 receptor (IGF-1R) in orbital fibroblasts leading to inflammation, deposition of hyaluronan and adipogenesis. The bone marrow may play an important role in autoimmune diseases, but its role in Graves' disease and TED is unknown. Here, we investigated whether induction of experimental Graves' disease and accompanying TED involves bone marrow activation and whether interference with IGF-1R signaling prevents this activation. Results: Immunization of mice with TSHR resulted in an increase the numbers of CD4-positive T-lymphocytes (p ≤0.0001), which was normalized by linsitinib (p = 0.0029), an increase of CD19-positive B-lymphocytes (p= 0.0018), which was unaffected by linsitinib and a decrease of GR1-positive cells (p= 0.0038), which was prevented by linsitinib (p= 0.0027). In addition, we observed an increase of Sca-1 positive hematopietic stem cells (p= 0.0007) and of stromal cell-derived factor 1 (SDF-1) (p ≤0.0001) after immunization with TSHR which was prevented by linsitinib (Sca-1: p= 0.0008, SDF-1: p ≤0.0001). TSHR-immunization also resulted in upregulation of CCL-5, IL-6 and osteopontin (all p ≤0.0001) and a concomitant decrease of the immune-inhibitory cytokines IL-10 (p= 0.0064) and PGE2 (p ≤0.0001) in the bone marrow (all p ≤ 0.0001). Treatment with the IGF-1R antagonist linsitinib blocked these events (all p ≤0.0001). We further demonstrate a down-regulation of arginase-1 expression (p= 0.0005) in the bone marrow in TSHR immunized mice, with a concomitant increase of local arginine (p ≤0.0001). Linsitinib induces an upregulation of arginase-1 resulting in low arginase levels in the bone marrow. Reconstitution of arginine in bone marrow cells in vitro prevented immune-inhibition by linsitinib. Conclusion: Collectively, these data indicate that the bone marrow is activated in experimental Graves' disease and TED, which is prevented by linsitinib. Linsitinib- mediated immune-inhibition is mediated, at least in part, by arginase-1 up-regulation, consumption of arginine and thereby immune inhibition. [ABSTRACT FROM AUTHOR]

Surgical crushing of stones alone has not addressed the increasing prevalence of kidney stones. A promising strategy is to tackle the kidney damage and crystal aggregation inherent in kidney stones with the appropriate therapeutic target. FKBP prolyl isomerase 5 (FKBP5) is a potential predictor of kidney injury, but its status in calcium oxalate (CaOx) kidney stones is not clear. This study attempted to elucidate the role and mechanism of FKBP5 in CaOx kidney stones. Lentivirus and adeno-associated virus were used to control FKBP5 expression in a CaOx kidney stone model. Transcriptomic sequencing and immunological assays were used to analyze the mechanism of FKBP5 deficiency in CaOx kidney stones. The results showed that FKBP5 deficiency reduced renal tubular epithelial cells (RTEC) apoptosis and promoted cell proliferation by downregulating BOK expression. It also attenuated cell–crystal adhesion by downregulating the expression of CDH4. In addition, it inhibited M1 polarization and chemotaxis of macrophages by suppressing CXCL10 expression in RTEC. Moreover, the above therapeutic effects were exerted by inhibiting the activation of NF-κB signaling. Finally, in vivo experiments showed that FKBP5 deficiency attenuated stone aggregation and kidney injury in mice. In conclusion, this study reveals that FKBP5 deficiency attenuates cell–crystal adhesion, reduces apoptosis, promotes cell proliferation, and inhibits macrophage M1 polarization and chemotaxis by inhibiting NF-κB signaling. This provides a potential therapeutic target for CaOx kidney stones. [ABSTRACT FROM AUTHOR]

When operated with a Hall effect thruster, either centrally or externally mounted, the hollow cathode discharge occurs in a magnetic field environment. Therefore, it is important to assess the influence of the magnetic field on the standalone operation of a hollow cathode to better predict device behavior when coupled with a Hall effect thruster. This study focuses on the influence of an applied axial magnetic field on the main oscillatory phenomena in the plume of a Kr-fed sub-ampere hollow cathode operated with an external disk anode. A probe array consisting of two cylindrical Langmuir probes and an emissive probe is used to assess changes in plasma parameters and collected ion saturation current as the magnetic field strength is varied up to 3 mT at the cathode's location. The electron transport along the cathode–anode space is analyzed in terms of total electron collision frequency. It is shown that a higher magnetic field strength induces larger plasma densities and lower electron temperatures. Applying a magnetic field to the discharge of a cathode operating in plume mode causes a reduction in both the ionization instability and ion acoustic turbulence (IAT) energies. This suggests a dampening of the main oscillatory phenomena in the plume of the hollow cathode. Furthermore, the total electron collision frequency and its main contributor, the anomalous collision frequency due to high-frequency IAT, decrease at higher field strengths. The results included in this communication are, to the best of the authors' knowledge, the first characterization of the response in low- and high-frequency wave content depending on a magnetic field in low-current hollow cathodes operating in standalone mode at < 1 A. [ABSTRACT FROM AUTHOR]

Kidney stone diseases are increasing globally in prevalence and recurrence rates, indicating an urgent medical need for developing new therapies that can prevent stone formation. One approach we have been working on is to develop small molecule inhibitors that can interfere with the crystallization process of the chemical substances that form the stones. For these drug discovery efforts, it is critical to have available easily accessible assay methods to evaluate the potential inhibitors and rank them for structure-activity relationship studies. Herein, we report a convenient, medium-to-high throughput assay platform using, as an example, the screening and evaluation of inhibitors of L-cystine crystallization for the prevention of kidney stones in cystinuria. The assay involves preparing a supersaturated solution, followed by incubating small volumes (<1 mL) of the supersaturated solution with test inhibitors for 72 hours, and finally measuring L-cystine concentrations in the supernatants after centrifugation using either a colorimetric or fluorometric method. Compared to traditional techniques for studying crystallization inhibitors, this miniaturized multi-well assay format is simple to implement, cost-effective, and widely applicable in determining and distinguishing the activities of compounds that inhibit crystallization. This assay has been successfully employed to discover L-cystine diamides as highly potent inhibitors of L-cystine crystallization such as LH708 with an EC50 of 0.058 µM, 70-fold more potent than L-CDME (EC50 = 4.31 µM). [ABSTRACT FROM AUTHOR]

Polymeric membranes have proven to be an effective method for the treatment of contaminated waters. Many factors influence their performances including the operating parameters, fabrication process and conditions, and their modifications using different additives. Introduced as additives, nanoparticles are capable of enhancing the membrane performance via their intrinsic properties which include their morphology, core size, and chemical nature. Nevertheless, some common problems such as nanoparticle agglomeration or leaching and the formation of defective areas, occur during the membrane fabrication. These issues depend on several factors which were observed to influence the membrane morphology and structure and consequently influence the treatment effectiveness. Accordingly, different strategies were investigated to avoid these issues. In this review paper, the effects of three different nanoparticles namely Titanium, Aluminum, and Silica on the performance of the modified membranes devoted to the treatment of organic waste streams will be thoroughly investigated. In addition, major effects related to the fabrication conditions including various challenges encountered during the membrane manufacturing and the different strategies used to improve performance will be thoroughly discussed. [ABSTRACT FROM AUTHOR]

Only 60-75% of conventional kidney stone surgeries achieve complete stone-free status. Up to 30% of patients with residual fragments <2 mm in size experience subsequent stone-related complications. Here we demonstrate a stone retrieval technology in which fragments are rendered magnetizable with a magnetic hydrogel so that they can be easily retrieved with a simple magnetic tool. The magnetic hydrogel facilitates robust in vitro capture of stone fragments of clinically relevant sizes and compositions. The hydrogel components exhibit no cytotoxicity in cell culture and only superficial effects on ex vivo human urothelium and in vivo mouse bladders. Furthermore, the hydrogel demonstrates antimicrobial activity against common uropathogens on par with that of common antibiotics. By enabling the efficient retrieval of kidney stone fragments, our method can lead to improved stone-free rates and patient outcomes. The success of surgical kidney stone removal is limited by the ability to efficiently retrieve stone fragments, resulting in incomplete stone clearance and subsequent morbidity. Here, the authors show the efficacy and biocompatibility of a magnetic hydrogel that selectively coats human kidney stone fragments in vitro allowing their total extraction using a magnetic wire. [ABSTRACT FROM AUTHOR]

It is desirable to attend to the mare at the time of foaling in order to assist fetal delivery and prevent complications. The early detection of the onset of labor is an important issue for the equine industry. The purpose of this study was to examine the applicability of a sensor for foaling detection using the data of surface temperature (ST), roll angle (rotation about the y-axis) and y-axis (long axis of the tail) acceleration which were collected from a multimodal device attached to the ventral tail base of the mare. The data were collected every 3 minutes in 17 pregnant mares. Roll angle differences from the reference values and the mare's posture (standing or recumbent) confirmed by video were compared and associated. Cohen's kappa coefficient was 0.99 when the threshold was set as ± 0.3 radian in roll angle differences. This result clearly showed that the sensor data can accurately distinguish between standing and recumbent postures. The hourly sensor data with a lower ST (LST < 35.5°C), a recumbent posture determined by the roll angle, and tail-raising (TR, decline of 200 mg or more from the reference value in y-axis acceleration) was significantly higher during the last hour prepartum than 2−120 hours before parturition (P < 0.01). The accuracy of foaling detection within one hour was verified using the following three indicators: LST; lying down (LD, change from standing to recumbent posture); and TR. When LST, LD and TR were individually examined, even though all indicators showed that sensitivity was 100%, the precision was 13.1%, 8.1% and 2.8%, respectively. When the data were combined as LST+LD, LST+TR, LD+TR and LST+LD+TR, detection of foaling improved, with precisions of 100%, 32.1%, 56.7% and 100%, respectively. In conclusion, the tail-attached multimodal device examined in this present study is useful for detecting foaling. [ABSTRACT FROM AUTHOR]

Background: Urolithiasis has been a major health concern for centuries, primarily owing to the limited treatment options in the physician's armamentarium. However, various studies have underscored a lesser incidence of urolithiasis in cohorts predominantly consuming fruits and vegetables. This article aims to review various dietary plants, medicinal herbs and phytochemicals in the prevention and management of urolithiasis. Methods: To provide context and evidence, relevant publications were identified on Google Scholar, PubMed and Science-Direct using keywords such as urolithiasis, nephrolithiasis, urolithiasis, renal stones, phytochemicals and dietary plants. Results: Growing bodies of evidence suggest the incorporation of plant-based foods, medicinal and herbal supplements, and crude drugs containing phytochemicals into the staple diet of people. The anti-urolithiatic activity of these plant bioactives can be attributed to their antioxidant, antispasmodic, diuretic, and inhibitory effect on the crystallization, nucleation and crystal aggregation effects. These mechanisms would help alleviate the events and symptoms that aid in the development and progression of renal calculi. In addition, it will also avoid the exacerbation of secondary disorders like inflammation and injury, which can initiate a vicious circle in turn worsening the disease progression. Conclusion: In conclusion, the results presented in the review demonstrate the promising role of various dietary plants, medicinal and herbal supplements, and phytochemicals in preventing and managing the precipitation of uroliths. However, more conclusive and cogent evidence from preclinical and clinical studies is required to substantiate their safety, efficacy and toxicity profiles in humans. Graphical Abstract This review encompasses various dietary plants, medicinal plants, herbal supplements and phytochemicals employed in the prevention and management of urolithiasis. The prime focus of this review is to summarize and critically review recent studies, observations, and inferences of these supplements, crude drugs and phytochemicals in urolithiasis. It also underscores various advantages, limitations and recent advances in research and development of the latter. [ABSTRACT FROM AUTHOR]

Background: Declines of the Eastern oyster, Crassostrea virginica, and its numerous ecological benefits have spurred oyster restoration initiatives. Successful restoration of a self-sustaining oyster population requires evaluating the temporal and spatial patterns of recruitment (settlement and survival) of oyster larvae in the target waterbody. Restoration of the Eastern oyster population in the Maryland Coastal Bays (MCBs), USA, a shallow lagoonal estuary, is of interest to federal, state, and non-governmental, but the location and timing of natural recruitment is not known. Methods: We assessed the spatial and temporal variation in oyster larval recruitment throughout the MCBs using horizontal ceramic tiles and PVC plates. Newly settled oyster larvae (recruits) were monitored biweekly from June to September 2019 and 2020 at 12 sites in the MCBs and a comparison site in Wachapreague, Virginia. Water quality measurements collected included temperature, salinity, dissolved oxygen, pH, and turbidity. The objectives of this study were to determine (1) the most effective substrate and design for monitoring oyster recruitment, (2) the spatial and temporal distribution of oyster larval recruitment in the MCBs, and (3) patterns in oyster larval recruitment that would be applicable to other lagoonal estuaries. Results: (1) Ceramic tiles were more effective than PVC plates for recruiting oyster larvae. (2) Peak settlement began during the period from late June through July, and oyster recruitment was greatest at sites closest to the Ocean City and Chincoteague inlets. (3) Areas near broodstock that have slow flushing rates to retain larvae may provide the best environments for recruitment of oysters to lagoonal estuaries. Discussion: As the first study on oyster larval recruitment in the MCBs, our results provide insight into their spatial and temporal distribution, methods that can serve as a foundation for future recruitment studies in other lagoonal estuaries, and baseline data that can be used to inform stakeholders and evaluate the success of oyster restoration projects in MCBs. [ABSTRACT FROM AUTHOR]

Introduction: The pathogenesis of infectious kidney stones is poorly understood. Bacteria have been implicated in promoting infectious stones via urease production; however, there is mounting evidence indicating the relationship is more complex. The aim of our study was to characterize suspected biotic and abiotic extrinsic factors that may modulate the formation of infectious stones. Materials and Methods: A high-throughput experimental model with Griffith's artificial urine was used to test a wide variety of urinary modulators and cytoplasmic enzymes present in crude cell-free extracts (CFEs) from bacterial strains to investigate how they impact struvite and calcium (Ca) phosphate crystal production. Crystal formation was evaluated with spectrophotometry and growth curve analysis. Light microscopy and scanning electron microscopy/X-ray diffraction was used for crystal structure and composition identification. Results: The acidic urinary modulators used in this study prevented crystal formation, whereas osteopontin had a significant inhibitory effect. Addition of CFEs from Proteus mirabilis 175A and 177A resulted in Ca phosphate and struvite crystals. Of interest, Klebsiella pneumoniae and Klebsiella oxytoca produced crystals including Ca phosphate and Ca oxalate, respectively. Pseudomonas aeruginosa had no urease production detected and produced Ca phosphate crystals. Discussion: Urinary modulators can have a wide variety of effects on infectious stone formation and the role of pH is important but does not guarantee robust crystal formation. Bacterial strains can produce Ca oxalate, Ca phosphate, and struvite stones with and without urease activity. Conclusion: Various urinary modulators appear to influence the process and are worthy of further evaluation as a potential therapeutic strategy to prevent infection-related urinary stone formation. Stones formed from urinary tract infections may be a result of multiple encoded metabolic pathways and discovering these would improve our understanding of the stone-bacterial relationship. [ABSTRACT FROM AUTHOR]

While clinical studies on acute phase proteins (APPs) have significantly increased in the last decade, and most commercial labs are now offering major APPs in their biochemical profiles, APP testing has not been widely adopted by veterinary clinical pathologists and veterinarians. Measurement of APP concentration is a useful marker for detecting the presence or absence of inflammation in cats with various diseases. APPs can also be reliably measured in different biological fluids (eg, effusions and urine) to improve their diagnostic utility. Measurement of APPs can be extremely beneficial in cats with feline infectious peritonitis (FIP) to discriminate between FIP and non‐FIP cats with similar clinical presentations. Additional benefits come from multiple and sequential measurements of APPs, particularly in the assessment of therapeutic efficacy. APPs are more sensitive than WBC counts for early detection of inflammation and to demonstrate an early remission or recurrence of the diseases. Given the potential utility of APPs, more studies are warranted, with a particular focus on the applications of APPs to guide the length of antimicrobial therapies, as suggested by the antimicrobial stewardship policy. New inflammatory markers have been discovered in human medicine, with a higher specificity for distinguishing between septic versus nonseptic inflammatory diseases. It is desirable that these new markers be investigated in veterinary medicine, to further test the power of APPs in diagnostic setting. [ABSTRACT FROM AUTHOR]

Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans. [ABSTRACT FROM AUTHOR]

Introduction: Osteopontin (OPN) is an integrin binding phosphorylated glycoprotein secreted by macrophages and leukocytes that is found in extracellular fluids and sites of inflammation; various forms of CD44 serve as receptors. Osteopontin, expressed by numerous cancers, enhances tumor progression and angiogenesis via the PI3K/AKT and ERK mediated pathways in concert with Vascular Endothelial Growth Factor (VEGF); OPN also plays a role in wound healing. The impact of minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) on plasma OPN levels is unknown. This study's goal was to assess blood levels during the first month after MICR. Method: Patients undergoing MICR for CRC who were enrolled in an IRB approved tissue/prospective data bank for whom preoperative, postop Day (POD) 1, POD 3, and at least 1 late postop plasma sample (POD 7–34) were available were studied. Osteopontin levels were determined in duplicate via enzyme linked immunosorbent assay (ELISA) (results reported as mean ± SD). The Wilcoxon signed rank test was used for analysis (significance P <.05). Results: A total of 101 CRC patients (63% colon and 37% rectal) met study criteria. The mean preop OPN level was 89.2 ± 36.8 (ng/ml) for the entire group. Significantly elevated (P <.001) mean plasma levels were detected, vs preop, on POD1 (198.0 ± 67.4; n = 101), POD 3 (186.0 ± 72.6, n = 101), POD 7–13 (154.1 ± 70.2, n = 70), POD14-20 (146.7 ± 53.4, n=32), and POD 21–27 (123.0 ± 56.9, n = 25). No difference was noted at the POD 27–34 timepoint (P >.05). Conclusion: Plasma OPN levels are significantly elevated over baseline for a month after MICR for CRC. The early rise in OPN levels may be related to the postop acute inflammatory response. The persistent elevation noted in weeks 2–4, however, may be a manifestation of wound healing in which OPN plays a role. Similar persistent plasma elevations of VEGF, angiopoietin 2 (ANG 2), and 11 other proangiogenic proteins have been noted and, collectively, may promote angiogenesis in residual tumors. [ABSTRACT FROM AUTHOR]

Lack of bone volume to place dental implants is frequently a problem in the reconstruction of edentulous patients. Even though autografts are the gold standard for jaw regeneration, morbidity associated with the harvesting site stimulates the demand for other substitutes. The aim of this study is to characterize the incorporation and the osteogenic ability of a viable cryopreserved human bone graft (VC-HBG) in the mandibular augmentation in rats. Bone chips from fresh human vertebrae cadaveric donors were processed, cryoprotected and deep-frozen at − 80 °C maintaining its cell viability. A jaw augmentation model was used in 20 athymic nude rats allocated into 2 groups to either receive the VC-HBG or an acellular graft as control (A-HBG). The assessment of the grafts' incorporation was performed at 4 and 8 weeks by micro-CT, histomorphometry and immunohistochemistry. Bone volume gain was significantly higher for the VC-HBG group at both time points. At 4 weeks, the A-HBG group presented significantly higher mineral density, but at 8 weeks, the VC-HBG group showed significantly higher values than the A-HBG. There was no statistical difference between VC-HBG and A-HBG groups at 4-weeks for remaining graft particles, while at 8 weeks, the VC-HBG group showed significantly less graft remnants. Collagen I, osteopontin and tartrate-resistant acid phosphatase expression were significantly higher in the VC-HBG group at both time points, while osteocalcin expression was significantly higher in the VC-HBG group at 8-weeks compared to the A-HBG group. This experimental research demonstrated that the VC-HBG shows positive osteogenic properties, greater bone formation, higher rate of bone remodeling and a better overall incorporation in rats' mandibles compared to the A-HBG. [ABSTRACT FROM AUTHOR]

The history of the European native oyster has been documented for numerous countries within its natural range. However, the history of Ostrea edulis in Wales remains conspicuously absent from current UK and European peer-reviewed publications. It was therefore deemed necessary to address this and as a result in-depth research of archival data was conducted including local trade directories, decennial census returns, collections from the National Museum Wales, annual government fisheries reports and grey literature from local historical societies. These historical reviews resulted in the construction of a timeline which documents all the significant historical dates related to O. edulis in Wales from the early 1500 s to present day. Fisheries statistics for England and Wales were also analysed for the western regional oyster fisheries in an attempt to understand the contribution which the Welsh landings made to the region. The review revealed that the Welsh fishery was the primary contributor of regional landings from the early 1600 s with maximum landings reported 1894, with the oyster beds at Mumbles producing more oysters than any other port until the fishery closed in 1937. A commercial native oyster fishery no longer exists in Wales but there remains a small native oyster population in South Wales. It is hoped that the historical accounts of bountiful catches, overexploitation, and restoration of O. edulis over the centuries in Wales may offer current conservation practitioners an insight into failures and mistakes of the past which could benefit the future of the European flat oyster in Wales. [ABSTRACT FROM AUTHOR]

Cystinuria is a genetic disease marked by recurrent kidney stone formation, usually at a young age. It frequently leads to chronic kidney disease. Treatment options for cystinuria have been limited despite comprehensive understanding of its genetic pathophysiology. Currently available therapies suffer from either poor clinical adherence to the regimen or potentially serious adverse effects. Recently, we employed atomic force miscopy (AFM) to identify l-cystine dimethylester (CDME) as an effective molecular imposter of l-cystine, capable of inhibiting crystal growth in vitro. More recently, we demonstrated CDME's efficacy in inhibiting l-cystine crystal growth in vivo utilizing a murine model of cystinuria. The application of AFM to discover inhibitors of crystal growth through structural mimicry suggests a novel approach to preventing and treating crystal diseases. [ABSTRACT FROM AUTHOR]

Despite its critical nature, the role of matrix in calcium oxalate stone formation is poorly understood. The wide diversity of proteins comprising matrix has contributed to the ambiguity. This study compares the protein distributions measured by mass spectrometry in human calcium oxalate stone matrix to that observed in cat stone matrix, because cats share many clinical characteristics of their stone disease with humans. The observed protein distributions were analyzed in the context of a recent model based on the aggregation of strongly anionic and strongly cationic proteins which includes selective adsorption of other proteins based on total charge. Matrix protein distributions shared many common features between species, including enrichment of both strongly anionic and strongly cationic proteins, increased total charge in matrix proteins compared to urine proteins, and a high degree of similarity of prominent strongly anionic proteins in the matrix of both species. However, there was weaker overlap of the specific dominant proteins in other regions of the net charge distribution. Collectively, these observations support the conceptual model where the strongly anionic proteins associate most strongly with the calcium oxalate crystal surfaces, while the other proteins associate with the strongly anionic proteins through non-specific, charge interactions with each other to create stones. Also, cats appear to be the best animal model of human stone disease identified to date based on these similarities. [ABSTRACT FROM AUTHOR]

Medication‐related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). Although bacterial infection is usually present, the etiology of MRONJ remains unknown. Here we apply a multimodal and multiscale (micro‐to‐nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ. A non‐necrotic bone sample was used as control. Both necrotic and non‐necrotic bone samples were collected from the jaw of a female individual affected by MRONJ after using BPs for 23 years. For the first time, resin cast etching was used to expose bacteria at the necrotic site. The bone–bacteria interface was also resolved at the nanoscale by scanning transmission electron microscopy (STEM). Nanosized particulates, likely corresponding to degraded bone mineral, were often noted in close proximity to or enclosed by the bacteria. STEM also revealed that the bone–bacteria interface is composed of a hypermineralized front fading into a highly disordered region, with decreasing content of calcium and phosphorus, as assessed by electron energy loss spectroscopy (EELS). This, combined with the variation in calcium, phosphorus, and carbon across the necrotic bone–bacteria interface evaluated by scanning electron microscopy (SEM)‐energy dispersive X‐ray spectroscopy (EDX) and the lower mineral‐to‐matrix ratio measured by micro‐Raman spectroscopy in necrotic bone, indicates the absence of a mineralization front in MRONJ. It appears that the bone–bacteria interface originates not only from uncontrolled mineralization but also from the direct action of bacteria degrading the bone matrix. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Extensive toxicology studies of synthetic vitreous fibers (SVFs) demonstrated that fiber dimension, durability/dissolution, and biopersistence are critical factors for risk of fibrogenesis and carcinogenesis. Lessons learned from the SVF experience provide useful context for predicting hazards and risk of nano-enabled advanced materials. This review provides (1) a historical toxicological overview of animal and in vitro toxicology studies of SVFs, (2) key findings that long durable fibers pose a risk of fibrogenic and tumorigenic responses and not short fibers or long soluble fibers, (3) in vitro and in vivo test methods for biodurability and biopersistence and associated predictive thresholds for fibrosis or tumors, and (4) recommendations for testing of advanced materials. Generally, SVFs (fiber lengths >20 µm) with in vitro fiber dissolution rates greater than 100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo fiber clearance less than WT1/2 40 or 50 days were not associated with fibrosis or tumors. Long biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. Fiber length-, durability-, and biopersistent-dependent factors that influence pathogenicity of mineral fibers are also expected to affect the biological effects of high aspect ratio nanomaterials (HARN). Only with studies aimed to correlate in vitro durability, in vivo biopersistence, and biological outcomes will it be determined whether similar or different in vitro fiber dissolution and in vivo half-life thresholds, which exempt carcinogenicity classification of SVFs, can also apply to HARNs. [ABSTRACT FROM AUTHOR]