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Reproductive Sciences (Thousand Oaks,... Jun 2024Atrazine (ATZ, CHClN) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways...
Atrazine (ATZ, CHClN) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways involved in hormone signaling, and DNA damage, and can cause reproductive disorders, including decreased fertility, and abnormal development of reproductive organs, as revealed in animal model studies. However, the effect of ATZ on steroidogenesis in the male reproductive system, especially reduction of ketosteroids to hydroxysteroids, remains unclear. This study investigated the toxicity of ATZ on the male reproductive system in the Wistar rat model, with an emphasis on its adverse effect on aldo-ketoreductase family 1 member C2 (AKR1C2). Male Wistar rats were administered ATZ for 56 days (duration of one spermatogenic cycle) through oral route, at 20, 40 and 60 mg/kg body weight (bw) doses. The results indicate that ATZ exposure affects the body weight, impairs sperm production, and decrease FSH, LH, and testosterone levels. Additionally, the down-regulation of key steroidogenic enzymes by ATZ disrupted the synthesis of testosterone, leading to decreased levels of this essential male hormone. On the other hand, the expression of AKR1C2 (mRNA and protein) in the testis was upregulated. The findings suggest that AKR1C2 plays a role in androgen metabolism. Furthermore, its overexpression may lead to alteration in the expression of genes in the connected pathway, causing an increase in the breakdown or inactivation of androgens, which would result in lower androgen levels and, thereby, lead to hypoandrogenism, as the combined effects of down-regulation of steroidogenic genes and up-regulation of AKR1C2. These findings reveal direct implication of disrupted AKR1C2 in male reproductive health and highlight the need for further research on the impact of environmental toxins on human fertility, ultimately providing for better patient care.
PubMed: 38943029
DOI: 10.1007/s43032-024-01627-3 -
Acta Diabetologica Jun 2024The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy...
The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy balance. Any form of weight loss dramatically affects the natural history of T2D, favoring prevention, treatment, and even remission in the case of significant weight loss. However, weight regain, which is often accompanied by the recurrence or worsening of obesity complications such as T2D, is an inevitable biological phenomenon that is an integral part of the pathophysiology of obesity. This can occur not only after weight loss, but also during obesity treatment if it is not effective enough to counteract the physiological responses aimed at restoring adiposity to its pre-weight-loss equilibrium state. Over the past few years, many controlled and randomized studies have suggested a superior efficacy of bariatric surgery compared to conventional therapy in terms of weight loss, glycemic control, and rates of T2D remission. Recently, the therapeutic armamentarium in the field of diabetology has been enriched with new antihyperglycemic drugs with considerable efficacy in reducing body weight, which could play a pathogenetic role in the remission of T2D, not through the classical incretin effect, but by improving adipose tissue functions. All these concepts are discussed in this position statement, which aims to deepen the pathogenetic links between obesity and T2D, shift the paradigm from a "simple" interaction between insulin resistance and insulin deficiency, and evaluate the efficacy of different therapeutic interventions to improve T2D management and induce diabetes remission whenever still possible.
PubMed: 38942960
DOI: 10.1007/s00592-024-02317-x -
Scientific Reports Jun 2024Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and...
Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and absorption thus resulting in low bioavailability. To overcome these drawbacks of OBB, amorphous spray-dried powders (ASDs) of OBB were formulated. The dissolution, characterizations, and pharmacokinetics of OBB-ASDs formulation were investigated, and its hepatoprotective action was disquisitive in the D-GalN/LPS-induced acute liver injury (ALI) mouse model. The characterizations of OBB-ASDs indicated that the crystalline form of OBB active pharmaceutical ingredients (API) was changed into an amorphous form in OBB-ASDs. More importantly, OBB-ASDs showed a higher bioavailability than OBB API. In addition, OBB-ASDs treatment restored abnormal histopathological changes, improved liver functions, and relieved hepatic inflammatory mediators and oxidative stress in ALI mice. The spray drying techniques produced an amorphous form of OBB, which could significantly enhance the bioavailability and exhibit excellent hepatoprotective effects, indicating that the OBB-ASDs can exhibit further potential in hepatoprotective drug delivery systems. Our results provide guidance for improving the bioavailability and pharmacological activities of other compounds, especially insoluble natural compounds. Meanwhile, the successful development of OBB-ASDs could shed new light on the research process of poorly soluble medicine.
Topics: Animals; Toll-Like Receptor 4; Mice; Biological Availability; Berberine; Male; Solubility; Liver; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Oxidative Stress; Protective Agents; Lipopolysaccharides; Powders; Drug Delivery Systems
PubMed: 38942824
DOI: 10.1038/s41598-024-65190-2 -
The Journal of Bone and Joint Surgery.... Jun 2024Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis....
BACKGROUND
Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA.
METHODS
All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c.
RESULTS
Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038).
CONCLUSIONS
This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m2. These findings may help surgeons risk-stratify this high-risk patient population.
LEVEL OF EVIDENCE
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
PubMed: 38941451
DOI: 10.2106/JBJS.23.01360 -
Medicine Jun 2024Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic... (Observational Study)
Observational Study
Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Neutrophils; Lymphocytes; Monocytes; Airway Resistance; Fatty Liver; Adult; Aged; Leukocyte Count; Lymphocyte Count
PubMed: 38941417
DOI: 10.1097/MD.0000000000038530 -
Medicine Jun 2024Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed... (Review)
Review
RATIONALE
Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease.
PATIENT CONCERNS
A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities.
DIAGNOSES
Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma.
INTERVENTIONS
A Sistrunk operation and ipsilateral thyroidectomy were performed.
OUTCOMES
Postoperative recovery was satisfactory.
LESSONS
Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.
Topics: Humans; Thyroglossal Cyst; Thyroid Neoplasms; Thyroid Cancer, Papillary; Female; Thyroidectomy; Male; Proto-Oncogene Proteins B-raf; Adult; Biopsy, Fine-Needle
PubMed: 38941410
DOI: 10.1097/MD.0000000000038540 -
IEEE Transactions on Bio-medical... Jun 2024The severity of atrial fibrillation (AF) can be assessed from intra-operative epicardial measurements (high-resolution electrograms), using metrics such as conduction...
OBJECTIVE
The severity of atrial fibrillation (AF) can be assessed from intra-operative epicardial measurements (high-resolution electrograms), using metrics such as conduction block (CB) and continuous conduction delay and block (cCDCB). These features capture differences in conduction velocity and wavefront propagation, but ignore complementary properties such as the morphology of the action potentials. In this work, we focus on such complementary properties, and derive features to detect variations in the atrial potential waveforms.
METHODS
We show that the spatial variation of atrial potential morphology during a single beat may be described by changes in the singular values of the epicardial measurement matrix. The method is non-parametric and requires little preprocessing. A corresponding singular value map points at areas subject to fractionation and block. Further, we developed an experiment where we simultaneously measure electrograms (EGMs) and a multi-lead ECG.
RESULTS
The captured data showed that the normalized singular values of the heartbeats during AF are higher than during SR, and that this difference is more pronounced for the (non-invasive) ECG data than for the EGM data, if the electrodes are positioned at favorable locations.
CONCLUSION
Overall, the singular value-based features are a useful indicator to detect and evaluate AF.
SIGNIFICANCE
The proposed method might be beneficial for identifying electropathological regions in the tissue without estimating the local activation time.
PubMed: 38941196
DOI: 10.1109/TBME.2024.3420412 -
IEEE Transactions on Bio-medical... Jun 2024In clinical ultrasound, current 2-D strain imaging faces challenges in quantifying three orthogonal normal strain components. This requires separate image acquisitions...
OBJECTIVE
In clinical ultrasound, current 2-D strain imaging faces challenges in quantifying three orthogonal normal strain components. This requires separate image acquisitions based on the pixel-dependent cardiac coordinate system, leading to additional computations and estimation discrepancies due to probe orientation. Most systems lack shear strain information, as displaying all components is challenging to interpret.
METHODS
This paper presents a 3-D high-spatial-resolution, coordinate-independent strain imaging approach based on principal stretch and axis estimation. All strain components are transformed into three principal stretches along three normal principal axes, enabling direct visualization of the primary deformation. We devised an efficient 3-D speckle tracking method with tilt filtering, incorporating randomized searching in a two-pass tracking framework and rotating the phase of the 3-D correlation function for robust filtering. The proposed speckle tracking approach significantly improves estimates of displacement gradients related to the axial displacement component. Non-axial displacement gradient estimates are enhanced using a correlation-weighted least-squares method constrained by tissue incompressibility.
RESULTS
Simulated and in vivo canine cardiac datasets were evaluated to estimate Lagrangian strains from end-diastole to end-systole. The proposed speckle tracking method improves displacement estimation by a factor of 4.3 to 10.5 over conventional 1-pass processing. Maximum principal axis/direction imaging enables better detection of local disease regions than conventional strain imaging.
CONCLUSION
Coordinate-independent tracking can identify myocardial abnormalities with high accuracy.
SIGNIFICANCE
This study offers enhanced accuracy and robustness in strain imaging compared to current methods.
PubMed: 38941195
DOI: 10.1109/TBME.2024.3420220 -
American Journal of Respiratory and... Jun 2024Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity....
Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors (MR) to promote inflammation. We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Using an established model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan) and MR (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis-generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Aldosterone was spontaneously produced by sarcoidosis PBMCs, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, PBMCs were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone or eplerenone, comparable to that of prednisone. The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses with important implications for clinical management.
PubMed: 38941161
DOI: 10.1164/rccm.202402-0265OC -
Gastric Cancer : Official Journal of... Jun 2024The contribution of the tumor microenvironment and extracellular matrix to the aggressive biology of Gastric Cancer (GC) has been recently characterized; however, the...
BACKGROUND
The contribution of the tumor microenvironment and extracellular matrix to the aggressive biology of Gastric Cancer (GC) has been recently characterized; however, the role of EMILIN-1 in this context is unknown. EMILIN-1 is an essential structural element for the maintenance of lymphatic vessel (LV) integrity and displays anti-proliferative properties as demonstrated in skin and colon cancer. Given the key role of LVs in GC progression, the aim of this study was to investigate the role of EMILIN-1 in GC mouse models.
METHODS
We used the syngeneic YTN16 cells which were injected subcutaneously and intraperitoneally in genetically modified EMILIN-1 mice. In alternative, carcinogenesis was induced using N-Methyl-N-nitrosourea (MNU). Mouse-derived samples and human biopsies were analyzed by IHC and IF to the possible correlation between EMILIN-1 expression and LV pattern.
RESULTS
Transgenic mice developed tumors earlier compared to WT animals. 20 days post-injection tumors developed in EMILIN-1 mutant mice were larger and displayed a significant increase of lymphangiogenesis. Treatment of transgenic mice with MNU associated with an increased number of tumors, exacerbated aggressive lesions and higher levels of LV abnormalities. A significant correlation between the levels of EMILIN-1 and podoplanin was detected also in human samples, confirming the results obtained with the pre-clinical models.
CONCLUSIONS
This study demonstrates for the first time that loss of EMILIN-1 in GC leads to lymphatic dysfunction and proliferative advantages that sustain tumorigenesis, and assess the use of our animal model as a valuable tool to verify the fate of GC upon loss of EMILIN-1.
PubMed: 38941035
DOI: 10.1007/s10120-024-01528-z