Severe Hyperplasia Research Articles

12408 Efnb2 Controls Pituitary Gland Development By Regulating Proliferation Of Pituitary Stem Cells

Abstract Disclosure: A. Gualtieri: None. L. Gomez-Corral: None. J. Nicholson: None. R. Tan: None. L. Guasti: None. C. Gaston-Massuet: None. Efnb2 encodes for the ligand Ephrinb2 that binds to its cognate Eph receptor, which plays an integral role in angiogenesis, stem cell regulation and tumorigenesis. Using a pituitary-specific Cre-driver (Hesx1Cre), we conditionally deleted Efnb2 from the early pituitary stem/progenitor cells (PSCs) of the developing pituitary gland. We found that Efnb2 is expressed in PSCs both during embryogenesis and adulthood, suggesting its involvement in PSCs maintenance. Here we show that genetic ablation of Efnb2 (Efnb2fl/fl;Hesx1Cre/+) results in severe pituitary hyperplasia, abnormal gland morphogenesis and delay in the terminal differentiation of hormone-producing cells. In order to understand the underlying molecular mechanisms by which Efnb2 deletion leads to pituitary abnormalities during embryogenesis, we performed transcriptomic analyses using mRNA-Seq at early stages of pituitary development on Efnb2+/+ and Efnb2−/− cell populations. Interestingly, unsupervised gene set enrichment analyses of the transcriptomic results identified Efnb2 as a key negative regulator of PSCs proliferation, whilst involved in the regulation of epithelial integrity and epithelial to mesenchymal transition (EMT). Functional assays performed to validate transcriptomic analyses revealed that Efnb2-null PSCs hyper-proliferate both in vitro and in vivo and downregulate the expression of genes involved in EMT, indicating a role of Efnb2 in these two developmental pathways. Indeed, whilst Efnb2-null PSCs within the marginal zone hyper-proliferate, they downregulate genes of epithelial integrity, resulting in an abnormal EMT transcriptomic profile. Additionally, these events lead to a significant delay of the pituitary cell lineage commitment program, leading to severe reduction in the expression of Pit1, Pomc1 and Gsu commitment markers. Taken together, our results reveal a novel role for Efnb2 (Ephrinb2) as key regulator of pituitary gland development. Efnb2 negatively regulates the proliferation of pituitary stem/progenitor cells controlling pituitary organ size while controlling the epithelial integrity of the stem cell niche. Presentation: 6/2/2024

Investigating dynamics, etiology, pathology, and therapeutic interventions of Caligus clemensi and Vibrio alginolyticus co-infection in farmed marine fish

This study investigated a disease outbreak characterized by caligid copepod infestations and subsequent secondary bacterial infections in European seabass (Dicentrarchus labrax) and flathead grey mullet (Mugil cephalus) cultivated at a private facility in the Deeba Triangle region of Egypt. Moribund fish displayed brown spots on the skin, tongue, and gills, along with lethargy and excess mucus. The fish suffered severe infections, exhibiting external hemorrhages, ulcers, and ascites. The fish had pale, enlarged livers with hemorrhaging. Comprehensive parasitological, bacteriological, molecular, immunity and histopathological analyses were conducted to identify the etiological agents and pathological changes. Caligid copepod infestation was observed in wet mounts from the buccal and branchial cavities of all examined fish, and the caligids were identified as Caligus clemensi through COI gene sequencing and phylogenetic analysis. Vibrio alginolyticus was confirmed as a secondary bacterial infection through biochemical tests, recA gene sequencing, and phylogenetic analyses. Antibiotic susceptibility testing revealed resistance to β-lactams, aminoglycosides, and trimethoprim-sulfamethoxazole in V. alginolyticus isolates. Upregulation of the inflammatory marker IL-1β in gill and skin tissues indicated a robust cell-mediated immune response against the pathogens. Histopathological examination revealed severe tissue damage, hyperplasia, hemorrhage, and congestion in the gills, along with hepatocellular degeneration and steatosis in the liver, providing initial insights into this outbreak. A comprehensive therapeutic regimen was implemented, comprising prolonged hydrogen peroxide immersion baths, followed by the application of the nature-identical plant-based compound Lice-less and probiotic Sanolife Pro-W supplementation. This integrated approach effectively eliminated C. clemensi infestations, controlled secondary bacterial infections, and restored fish health, reducing morbidity and mortality rates to minimal levels.

Model Predicting the Risk of Endometrial Hyperplasia Developing into Endometrial Cancer.

This study retrospectively analyzed the medical records of 200 patients with endometrial hyperplasia to predict the risk of concurrent endometrial cancer. Patients were categorized into either the endometrial cancer group or the endometrial hyperplasia group based on post-hysterectomy pathology. The investigation compared general information, tumor indices, fertility history, preoperative endometrial sampling methods, comorbidities, and clinical symptoms between the groups to identify risk factors for endometrial hyperplasia complicating endometrial cancer. (1) Of the 200 patients, 68 (34.0%) were diagnosed with concurrent endometrial cancer post-hysterectomy. Among these, 60 (88.24%) had endometrioid adenocarcinoma, while 8 (11.76%) had other types. Stage I was identified in 58 patients (85.29%) and Stage II in 10 patients (14.71%). High differentiation was observed in 57 cases (83.82%), moderate differentiation in 7 cases (10.29%), and poor differentiation in 4 cases (5.89%), indicating that most endometrial cancers complicated by hyperplasia were early-stage, well-differentiated endometrioid carcinomas; (2) Univariate analysis revealed statistically significant differences in age, menopausal status, length of menopause, and preoperative endometrial pathology of severe atypical hyperplasia between the groups; (3) Multivariate analysis indicated significant differences for age ≥ 53.5 years (OR: 4.307, 95% CI: 2.018-9.192, p < 0.05), menopausal status (OR: 5.250, 95% CI: 2.449-11.252, p < 0.05), and severe atypical endometrial hyperplasia (OR: 4.817, 95% CI: 1.260-18.419, p < 0.05); (4) Significant differences were observed among patients with endometrial hyperplasia when stratified by the presence of zero, one, two, or three high-risk factors. In conclusion, patients aged ≥ 53.5 years, those who are menopausal, and those with severe atypical endometrial hyperplasia preoperatively are at higher risk for endometrial cancer. The risk increases with the number of high-risk factors present in patients with atypical endometrial hyperplasia.

Editorial Comment: Complex Buccal Graft Urethroplasty Combined With HoLEP in the Setting of Concomitant Urethral Stricture Disease and Severe Benign Prostatic Hyperplasia: A Case Report

Editorial Comment: Complex Buccal Graft Urethroplasty Combined With HoLEP in the Setting of Concomitant Urethral Stricture Disease and Severe Benign Prostatic Hyperplasia: A Case Report

Winter mortality of freshwater fish associated with parasitic infection

This study reports an episode of fish mortality occurred in the Garupá and Pindapoy Grande streams, near the confluence with the Paraná River (Garupá, Argentina). Dead and moribund fish of various species were observed floating on the water surface. Environmental parameters measured were temperature 5 °C, water temperature 15.1 (±0.6) °C, dissolved oxygen 8.7 (±1.2) ppm, pH 7.5 (±0.2), electrical conductivity 67.6 (± 8.8) mS cm-1 and mean depth of 1.7 (±1.0) m. Macroscopic examination of moribund fish revealed corneal opacity, whitish tegument, increased gill mucus, and whitish areas on gill filaments. Microscopic analysis of gills revealed severe generalized epithelial hyperplasia, lamellar fusion, congestion, and inflammatory infiltrate, particularly lymphocytes and eosinophilic granular cells. In addition, microscopic examination allowed the identification of the following ectoparasites found in gills and tegument: Chilodonella, Ichthyophthirius, Dactylogyridae and Trichodinidae, representing 98%, 1.2%, 0.6% and 0.2%, respectively. This study constitutes a novel record of wild fish mortality associated with extreme environmental conditions and parasitosis. Furthermore, our findings are significant as there are no prior reports in Argentina of epizootic cases linked to Chilodonella sp. infection in wild or farmed fish populations, being the first report of chilodonelliasis for this region.

Complex Buccal Graft Urethroplasty Combined With HoLEP in the Setting of Concomitant Urethral Stricture Disease and Severe Benign Prostatic Hyperplasia: A Case Report

Background: Urethral strictures and benign prostatic hyperplasia (BPH) are 2 common causes of urinary obstruction and urinary emptying symptoms. While urethroplasty and endoscopic management of BPH have been extensively discussed in the literature when performed on their own, a case of simultaneous urethroplasty and endoscopic management of BPH has not been previously described in the literature. Case Description: We present the case of a 75-year-old man with significant BPH and concomitant bulbar obliterative urethral stricture. After discussion of treatment options with the patient, we elected to perform both holmium LASER enucleation of the prostate (HoLEP) of a 200cc prostate and buccal graft urethroplasty during the same surgery. The HoLEP was performed through a dorsal urethrotomy in anticipation of urethroplasty. Nontransecting anastomotic repair was then combined with the buccal graft urethroplasty. The patient did not have any acute postoperative complications and had no recurrence. He reported improvements in outcome questionnaire scores and uroflow parameters at the 12-month follow-up. Conclusions: This case presentation is the first to report on simultaneous complex urethroplasty and endoscopic management of BPH, specifically HoLEP. It shows that this approach can lead to positive urinary outcomes without added complications and with lasting outcomes, thereby allowing the use of a combined surgical approach.

Abstract 1147: Crosstalk Between Alk5 And Mtorc1 Signaling Promotes VSMC Differentiation And The Therapeutic Effect Of Rapamycin

Background: Vascular smooth muscle cells (VSMC) phenotypic switching contributes to vascular repair and remodeling but also to pathologies including intimal hyperplasia. The mTORC1 inhibitor rapamycin is an effective drug-eluting stent agent that promotes VSMC differentiation. TGFβ also promotes VSMC differentiation through SMAD transcription factors. We investigated unexpected convergence between these pathways in VSMC plasticity. Methods: We assessed the interactions between rapamycin and the TGFβ1 (ALK5) signaling in human coronary artery SMCs and in vascular remodeling using inducible SMC-specific knockout mice (ALK5iKO). Results: Genome-wide histone H3K27 acetylation analysis unexpectedly identified SMAD binding elements as the motif most enriched after rapamycin treatment of hCASMCs. Treatment with rapamycin promoted rapid phosphorylation of SMAD2/3. Extensive signaling studies revealed that this phosphorylation required ALK5 activity but not TGF-β ligand. Surprisingly, ALK5 and SMAD2/3 were required for rapamycin-induced differentiation. We determined that rapamycin relieves FKBP12 inhibition of ALK5 to promote ligand independent Smad signaling, and FKBP12 knockdown was sufficient to induce contractile genes. Notably, rapamycin treatment induced an interaction between TET2 and SMAD2/3, and these SMADs were required for differentiation-associated chromatin remodeling, including DNA hydroxymethylation and H3K27 acetylation at contractile genes, suggesting that SMADs and TET2 function in concert at SBE- and CArG-containing promoter regions. Furthermore, ALK5iKO mice exhibited severe intimal hyperplasia after carotid artery injury compared to controls and were entirely resistant to the therapeutic effect of rapamycin, despite persistent inhibition of mTORC1. Consistent with in vitro findings, treatment with rapamycin elevated pSmad3 staining post-injury in the medial layer of control but not ALK5iKO mice. Conclusions: We report the surprising observation that rapamycin requires FKBP12/ALK5/SMAD2/3 signaling in order to promote TET2-dependent chromatin remodeling and SMC differentiation. Understanding these mechanisms may reveal new therapeutic strategies for treating vascular diseases.

A systematic review and network meta-analysis comparing Rezūm with transurethral needle ablation and microwave thermotherapy for the management of enlarged prostate.

We aim to compare efficacy and safety of water vapour therapy (Rezūm), transurethral needle ablation (TUNA) and transurethral microwave therapy (TUMT) for treating men with moderate to severe benign prostatic hyperplasia (BPH) symptoms. PubMed/MEDLINE, EMBASE and Cochrane Library were searched from inception to 30 July 2023, followed by reference searching and dual-independent study selection. We analysed only randomized clinical trials. RoB-2, NIH-quality assessment tool and GRADE guidelines were used for quality-of-evidence (QoE) assessment. Relevant prospective studies without a critical risk-of-bias were included. At 12 months, Rezūm showed similar efficacy to TUNA and TUMT for improvement in International Prostate Symptoms Score - Rezūm versus TUMT: 1.33 points (95% CI: -1.66 to 4.35) favouring TUMT (QoE: Moderate) and Rezūm versus TUNA: 0.07 points (95% CI: -3.64 to 3.88) favouring TUNA (QoE: Low). Rezum had similar outcomes to TUNA and TUMT for Maximum Peak-Flow Rate (Qmax): Rezūm versus TUMT: 1.05 mL/s (95% CI: -4.88 to 2.82) favouring Rezūm (QoE: Low) and Rezūm versus TUNA: 0.37 mL/s (95% CI: -4.61 to 4.21) favouring TUNA (QoE: Low). Furthermore, post-void residual volume (PVR) comparisons demonstrated that Rezūm was similar, or inferior to other techniques at 12 months - Rezūm versus TUMT: 11.20 mL (95% CI: -32.40 to 10.30) favouring TUMT (QoE: Low) and Rezūm versus TUNA: 24.10mL (95% CI: 2.81 to 45.10) favouring TUNA (QoE: Low). Rezūm also had a similar surgical retreatment rate with TUMT and TUNA up to 3-years - TUMT versus Rezūm RR: 1.21 (95% CI: 0.20 to 15.90) (QoE: Low) and TUNA versus Rezūm showed RR: 1.81 (95% CI: 0.2 to 24.60) (QoE: Low). In the first 12months after treatment, Rezūm had a higher rate of serious adverse events (Clavien-Dindo ≥ Grade 3) than TUMT and TUNA. TUMT versus Rezūm with RR = 0.53 (95% CI: 0.13 to 3.14) (QoE: Low) and TUNA versus Rezūm with RR = 0.38 (95% CI: 0.04 to 3.49) (QoE: Low). Moderate to weak evidence suggests that Rezūm is not superior to TUNA and TUMT in all domains studied.

Impact of sub-chronic polystyrene nanoplastics exposure on hematology, histology, and endoplasmic reticulum stress-related protein expression in Nile tilapia (Oreochromis niloticus)

Nanoplastics (NPs) are one of the most hazardous marine litters, having the potential to cause far-reaching impacts on the environment and humankind. The effect of NPs on fish health has been studied, but their impact on the subcellular organelles remains unexplored. The present investigation studied the possible implications of polystyrene-nanoplastics (PS-NPs) on the hematology, tissue organization, and endoplasmic reticulum (ER) stress-related proteins in Nile tilapia (Oreochromis niloticus). Fish were exposed to ∼100 nm PS-NPs at environmentally relevant (0.1 mg/L), and sublethal (1, 10 mg/L) concentrations for 14 days through water exposure. The growth performance and hematological parameters such as erythrocytes, hemoglobin, hematocrit, and leucocytes decreased, while thrombocytes increased with PS-NPs dose-dependently. The gills, liver, kidney, and heart tissues displayed increasing degrees of pathology with increased concentrations of PS-NPs. The gills showed severe epithelial hyperplasia and lamellar fusion. The liver had an abstruse cellular framework, membrane breakage, and vacuolation. While glomerular and tubular atrophy was the most prominent pathology in the kidney tissue, the heart displayed extensive myofibrillar loss and disorderly arranged cardiac cells. The ER-stress-related genes such as bip, atf6, ire1, xbp1, pkr, and apoptotic genes such as casp3a, and bax were over-expressed, while, the anti-apoptotic bcl2 was under-expressed with increasing concentrations of PS-NPs. Immunohistochemistry and blotting results of GRP78, CHOP, EIF2S, and ATF6 in gills, liver, kidney, and heart tissues affirmed the translation to ER stress proteins. The results revealed the sub-lethal adverse effects and the activation of the ER-stress pathway in fish with sub-chronic exposure to PS-NPs.

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns

Colonic crypt stem cell functions are controlled by tight junction protein claudin-7 through Notch/Hippo signaling.

The tight junction protein claudin-7 is essential for tight junction function and intestinal homeostasis. Cldn7 deletion in mice leads to an inflammatory bowel disease-like phenotype exhibiting severe intestinal epithelial damage, weight loss, inflammation, mucosal ulcerations, and epithelial hyperplasia. Claudin-7 has also been shown to be involved in cancer metastasis and invasion. Here, we test our hypothesis that claudin-7 plays an important role in regulating colonic intestinal stem cell function. Conditional knockout of Cldn7 in the colon led to impaired epithelial cell differentiation, hyperproliferative epithelium, a decrease in active stem cells, and dramatically altered gene expression profiles. In 3D colonoid culture, claudin-7-deficient crypts were unable to survive and form spheroids, emphasizing the importance of claudin-7 in stem cell survival. Inhibition of the Hippo pathway or activation of Notch signaling partially rescued the defective stem cell behavior. Concurrent Notch activation and Hippo inhibition resulted in restored colonoid survival, growth, and differentiation to the level comparable to those of wild-type derived crypts. In this study, we highlight the essential role of claudin-7 in regulating Notch and Hippo signaling-dependent colonic stem cell functions, including survival, self-renewal, and differentiation. These new findings may shed light on potential avenues to explore for drug development in colorectal cancer.

PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration

We investigated a syndromic disease comprising blindness and neurodegeneration in 11 Saarlooswolfdogs. Clinical signs involved early adult onset retinal degeneration and adult-onset neurological deficits including gait abnormalities, hind limb weakness, tremors, ataxia, cognitive decline and behavioral changes such as aggression towards the owner. Histopathology in one affected dog demonstrated cataract, retinal degeneration, central and peripheral axonal degeneration, and severe astroglial hypertrophy and hyperplasia in the central nervous system. Pedigrees indicated autosomal recessive inheritance. We mapped the suspected genetic defect to a 15 Mb critical interval by combined linkage and autozygosity analysis. Whole genome sequencing revealed a private homozygous missense variant, PCYT2:c.4A>G, predicted to change the second amino acid of the encoded ethanolamine-phosphate cytidylyltransferase 2, XP_038402224.1:(p.Ile2Val). Genotyping of additional Saarlooswolfdogs confirmed the homozygous genotype in all eleven affected dogs and demonstrated an allele frequency of 9.9% in the population. This experiment also identified three additional homozygous mutant young dogs without overt clinical signs. Subsequent examination of one of these dogs revealed early-stage progressive retinal atrophy (PRA) and expansion of subarachnoid CSF spaces in MRI. Dogs homozygous for the pathogenic variant showed ether lipid accumulation, confirming a functional PCYT2 deficiency. The clinical and metabolic phenotype in affected dogs shows some parallels with human patients, in whom PCYT2 variants lead to a rare form of spastic paraplegia or axonal motor and sensory polyneuropathy. Our results demonstrate that PCYT2:c.4A>G in dogs cause PCYT2 deficiency. This canine model with histopathologically documented retinal, central, and peripheral neurodegeneration further deepens the knowledge of PCYT2 deficiency.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy

PurposeTo explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients.Materials and methodsA consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided.ResultsAll of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths.ConclusionThe technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Assessment of Histopathological Alterations and Oxidative Stress in the Liver and Kidney of Male Rats following Exposure to Aluminum Chloride.

The study aims to investigate the residual and histopathological effects of chronic aluminum chloride (AlCl3) toxicity in the kidney and liver of male rats. After 30-, 60-, and 90-day exposure period, analyses were conducted to assess the toxicity in the kidney and liver. The results showed that the concentration of AlCl3 in the kidney and liver increased significantly in 30-, 60-, and 90-day periods. The effects of oxidative stress on the kidneys and liver were dose- and time-dependent. Levels of malondialdehyde (MDA) significantly increased when exposed to AlCl3 groups. Conversely, the activity of antioxidant parameters, including reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), significantly decreased in the AlCl3 exposed groups, indicating compromised oxidant mechanisms. Both the kidney and liver exhibited severe tissue damage, including necrosis, fibrosis, and inflammatory cell infiltration, in rats exposed to AlCl3. Kidney sections showed hyperplasia of the epithelial cells lining the renal tubules, resembling finger-like structures. Liver sections displayed severe lobular hyperplasia and an increase in mitotic figures. Our study suggests that AlCl3 has a detrimental impact on these vital organs and emphasizes the importance of monitoring and mitigating aluminum exposure, particularly where it is present in high concentration.

Intraoperative changes of surgical approach and a second surgery after percutaneous endoscopic surgery for lumbar spinal stenosis

ObjectiveTo investigate the reasons for a second surgery after Percutaneous Endoscopic Surgery (PES) for lumbar spinal stenosis and to provide references for the choice of indications and appropriate surgical approach. MethodA total of 426 patients received PES for lumbar spinal stenosis. The postoperative, intraoperative, and postoperative data of the subjects were analyzed. The reasons for intraoperative difficulties, poor outcomes after surgery, and a second surgery were analyzed. ResultThe surgical approach was changed in four out of 426 patients (0.94 %) during surgery, and 6 patients (1.4 %) received a second surgery; 3 out of 4 patients were intraoperatively shifted to PIED using the Delta endoscope, and 1 shifted to ordinary PIED. The reasons for the intraoperative change of surgical approach included severe hyperplasia and obscure anatomic structure in 3 patients and a dural sac tear with neural outflow in 1 patient. The reasons for a second surgery in 19 patients were as follows: nerve entrapment by bone fragments in 1 patient; nerve injury in 3 patients; lumbar instability in 3 patients; untreated or residual Lumbar Intervertebral Disc Herniation (LIDH) in 4 patients; recurrent LIDH in 1 patient; and inadequate decompression in 7 patients. ConclusionSevere hyperplasia, obscure anatomic structure, lumbar instability, and nerve injury are the common reasons for a second surgery after PES for lumbar spinal stenosis. Appropriate indications and surgical approaches can be chosen based on the patient's situations and technical conditions.

Tertiary Hyperparathyroidism and Extra Skeletal Calcification in End Stage Kidney Disease Patients: Case-series and Literature Review

Background:: Tertiary hyperparathyroidism (THPT) is a well-known complication of end-stage kidney disease (ESKD), resulting from a loss of functional renal tissue with subsequent alterations in calcium and phosphate metabolism. Tertiary hyperparathyroidism reflects severe parathyroid hyperplasia with autonomous excessive secretion of parathyroid hormone (PTH) that is no longer responsive to the concentration of plasma calcium and leads to abnormal bone remodelling, soft tissue calcifications, vasculopathy, and other systemic complications. Case Presentation:: The authors, hereby, highlight varied presentations of tertiary hyperparathyroidism (THPT) by presenting 3 interesting cases, describing their clinical course and outcomes. Through sharing these experiences and insights, we hope to contribute to a better understanding of THPT and its optimal management in patients with ESKD. Conclusion:: THPT can have a significant impact on patient health and quality of life. Despite the widespread use of interventions, such as vitamin D analogues, calcimimetics and parathyroidectomy, THPT remains a significant clinical challenge for patients with ESKD.

Common salt aggravated pathology of testosterone-induced benign prostatic hyperplasia in adult male Wistar rat

BackgroundBenign prostatic hyperplasia (BPH) is a major health concern associated with lower urinary tract symptoms and sexual dysfunction in men. Recurrent inflammation, decreased apoptotic rate and oxidative stress are some of the theories that explain the pathophysiology of BPH. Common salt, a food additive, is known to cause systemic inflammation and redox imbalance, and may serve as a potential risk factor for BPH development or progression. This study examined the effect of common salt intake on the pathology of testosterone-induced BPH.MethodsForty male Wistar rats were randomly divided into four equal groups of 10: a control and three salt diet groups-low-salt diet (LSD), standard-salt diet (SSD) and high-salt diet (HSD). The rats were castrated, allowed to recuperate and placed on salt-free diet (control), 0.25% salt diet (LSD), 0.5% salt diet (SSD) and 1.25% salt diet (HSD) for 60 days ad libitum. On day 33, BPH was induced in all the rats with daily injections of testosterone propionate-Testost® (3 mg/kg body weight) for 28 days. The rats had overnight fast (12 h) on day 60 and were euthanized the following day in order to collect blood and prostate samples for biochemical, molecular and immunohistochemistry (IHC) analyses. Mean ± SD values were calculated for each group and compared for significant difference with ANOVA followed by post hoc test (Tukey HSD) at p < 0.05.ResultsThis study recorded a substantially higher level of IL-6, IL-8 and COX-2 in salt diet groups and moderate IHC staining of COX-2 in HSD group. The prostatic level of IL-17, IL-1β, PGE2, relative prostate weight and serum PSA levels were not statistically different. The concentrations of IGF-1, TGF-β were similar in all the groups but there were multiple fold increase in Bcl-2 expression in salt diet groups-LSD (13.2), SSD (9.5) and HSD (7.9) and multiple fold decrease in VEGF expression in LSD (-6.3), SSD (-5.1) and HSD (-14.1) compared to control. Activity of superoxide dismutase (SOD) and concentration of nitric oxide rose in LSD and SSD groups, and SSD and HSD groups respectively. Activities of glutathione peroxidase and catalase, and concentration of NADPH and hydrogen peroxide were not significantly different. IHC showed positive immunostaining for iNOS expression in all the groups while histopathology revealed moderate to severe prostatic hyperplasia in salt diet groups.ConclusionsThese findings suggest that low, standard and high salt diets aggravated the pathology of testosterone-induced BPH in Wistar rats by promoting inflammation, oxidative stress, while suppressing apoptosis and angiogenesis.

Effect of Usnea longissima ethyl acetate extract on acute oxidative and inflammatory lung damage from Staphylococcus aureus infection in rats.

The role of oxidants and proinflammatory cytokines in the pathogenesis of pneumonia caused by Staphylococcus aureus (S. aureus) has been demonstrated. The present study aims to investigate the protective effect of ethyl acetate extract (EtOAc) obtained from Usnea longissima (UL) against acute oxidative and inflammatory lung damage due to S. aureus infection in rats. Albino Wistar-type male rats were divided into three groups: Healthy (HG), S. aureus inoculated (SaG), and S. aureus inoculated + ULEtOAc administered (SUL). SaG (n = 6) and SUL (n = 6) group rats' left nostrils (excluding HG) were inoculated with 0.1 ml bacterial mixture. After 24 hours, ULEtOAc (50 mg/kg) was administered orally to the SUL group, and the same volume of normal saline was administered orally to the HG (n = 6) and SaG groups. This procedure was performed once a day for seven days. Levels of oxidant and antioxidant parameters such as malondialdehyde (MDA) and total glutathione (tGSH), as well as pro-inflammatory cytokine levels such as nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), were measured in removed lung tissues. Tissues were also examined histopathologically. Biochemical results showed that ULEtOAc significantly suppressed the increase of MDA, NF-κB, TNF-α, and IL-1β levels and the decrease of tGSH caused by S. aureus in lung tissue. S. aureus inoculation caused severe mononuclear cell infiltration in interstitial areas, severe lymphoid hyperplasia in bronchial-associated lymphoid tissue and severe alveolar edema, histopathologically. Treatment with ULEtOAc had an attenuating effect on these histopathological findings. Experimental results from this study suggest that ULEtOAc may be beneficial in treating S. aureus-induced oxidative and inflammatory lung damage.

Single-port Transvesical Robot-Assisted Simple Prostatectomy: Surgical Technique and Clinical Outcomes

BackgroundSurgical management of large prostatic adenomas can be performed via open, endoscopic, or robotic approaches. A low-profile single-port (SP) robot was built to work in confined areas (ie, the bladder) and regionalize surgery. ObjectiveTo describe the novel SP transvesical (TV) robot-assisted simple prostatectomy (RASP) and report clinical outcomes. Design, setting, and participantsSP TV RASP cases were performed in an academic hospital by two surgeons from 2019 to 2023. A total of 117 cases were performed, and data from patients with at least 12 mo of follow-up were analyzed. The inclusion criterion was severe obstructive urinary symptoms or catheter-dependent urinary retention due to large prostates with volume >80 ml. Surgical procedureThe procedure consisted of two main steps through a single 3-cm suprapubic incision: first, enucleation of the adenoma, and second, a 360° bladder mucosal flap reconstruction. No drains or continuous bladder irrigation was used routinely. MeasurementsIntraoperative parameters, pre- and postoperative uroflowmetry, and 1-yr clinical outcomes were assessed. We used descriptive statistics to analyze the data. Results and limitationsAll procedures were completed successfully without additional ports or conversions. The median console time and estimated blood loss were 107 min and 100 ml, respectively. Transfusion rate was 0%. Intraoperative complications included two suspected air emboli attributed to high insufflation pressures. There were no major postoperative complications. In total, 95.8% were discharged within the first 24 h, with a median length of stay and pain score of 5 h and 3/10, respectively. There was persistent improvement in the median International Prostate Symptom Score and flow rate after 1 yr. The median Sexual Score Inventory for Men score was 20 at 12 mo. Our study is limited by its retrospective nature and cohort size. ConclusionsSP TV RASP is a feasible alternative for the management of severe benign prostatic hyperplasia that promotes fast recovery and demonstrates 1-yr improvement in urinary function. Patient summarySingle-port transvesical robot-assisted simple prostatectomy is a minimally invasive alternative for the treatment of large benign prostatic growth. A single robotic arm goes through a small incision in the skin and bladder to extract the obstructive prostatic tissue. Afterward, reconstruction of the area is done to decrease bleeding and improve postoperative symptoms. We found that patients recover quickly and have excellent clinical results with a low risk of complications.

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway

ObjectiveHepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms. MethodsThe active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot. ResultsDifferent CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers. ConclusionOur data supported that different CX extracts, especially CXAL and CXPHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.