NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage.

Proteasome inhibitors have been applied to anticancer therapy by accumulating toxic misfolded proteins. However, chemical inactivation of proteasome generates aggresome, a Vimentin cage-enclosed subcellular structure quarantining HDAC6-Dynein-transported misfolded proteins before the protein toxicants are degraded by autophagy. Hence, aggresome may attenuate proteasome inhibitor drugs-induced cytotoxicity. To solve the problem, it is imperative to characterize how cells assemble aggresome. By examining aggresomes in six cell lines, A549 cells were selectively studied for their bigger cell size and moderate aggresome forming activity. Aggresome grew in size upon continuous exposure of A549 cells to proteasome inhibitor MG132, and reached a mature size around 16th to 24th hour of treatment. Mechanistic studies revealed that NF-кB translocated to nucleus in MG132 treated cells, and chemical activation or knockdown of NF-кB enhanced or prohibited aggresome assembly. Further analyses showed that NF-кB upregulated HDAC6, and HDAC6 maintained Vimentin cage by interacting with Vimentin p72, a key modification of the intermediate filament contributing to aggresome formation. Remarkably, chemical inactivation of NF-кB synergized MG132-induced cell mortality. All the findings suggest that NF-кB dictates aggresome assembly via upregulating HDAC6, and NF-кB inhibitor may serve as a potential drug potentiating proteasome inhibitor medicine-induced cytotoxicity during the treatment of cancer cells.

High-intensity interval training vs. yoga in improving binge eating and physical fitness in inactive young females.

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (- 20.25%, p = 0.006, ηp2 = 0.408), fat mass (FM, - 3.13%, p = 0.033, ηp2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, ηp2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, - 1.78%, p = 0.006, ηp2 = 0.433), FM (- 3.94%, p = 0.033, ηp2 = 0.285), and BMI (- 1.80%, p = 0.006, ηp2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, ηp2 = 0.088; YG: 11.90%, p = 0.009, ηp2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, ηp2 = 0.03) and CG (11.91%, p = 0.022, ηp2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

The changing scenario of drug discovery using AI to deep learning: Recent advancement, success stories, collaborations, and challenges.

Due to the transformation of artificial intelligence (AI) tools and technologies, AI-driven drug discovery has come to the forefront. It reduces the time and expenditure. Due to these advantages, pharmaceutical industries are concentrating on AI-driven drug discovery. Several drug molecules have been discovered using AI-based techniques and tools, and several newly AI-discovered drug molecules have already entered clinical trials. In this review, we first present the data and their resources in the pharmaceutical sector for AI-driven drug discovery and illustrated some significant algorithms or techniques used for AI and ML which are used in this field. We gave an overview of the deep neural network (NN) models and compared them with artificial NNs. Then, we illustrate the recent advancement of the landscape of drug discovery using AI to deep learning, such as the identification of drug targets, prediction of their structure, estimation of drug-target interaction, estimation of drug-target binding affinity, design of de novo drug, prediction of drug toxicity, estimation of absorption, distribution, metabolism, excretion, toxicity; and estimation of drug-drug interaction. Moreover, we highlighted the success stories of AI-driven drug discovery and discussed several collaboration and the challenges in this area. The discussions in the article will enrich the pharmaceutical industry.

Recent Advances in Fire-Retardant Silicone Rubber Composites.

Silicone rubber (SR), as one kind of highly valuable rubber material, has been widely used in many fields, e.g., construction, transportation, the electronics industry, automobiles, aviation, and biology, owing to its attractive properties, including high- and low-temperature resistance, weathering resistance, chemical stability, and electrical isolation, as well as transparency. Unfortunately, the inherent flammability of SR largely restricts its practical application in many fields that have high standard requirements for flame retardancy. Throughout the last decade, a series of flame-retardant strategies have been adopted which enhance the flame retardancy of SR and even enhance its other key properties, such as mechanical properties and thermal stability. This comprehensive review systematically reviewed the recent research advances in flame-retarded SR materials and summarized and introduced the up-to-date design of different types of flame retardants and their effects on flame-retardant properties and other performances of SR. In addition, the related flame-retardant mechanisms of the as-prepared flame-retardant SR materials are analyzed and presented. Moreover, key challenges associated with these various types of FRs are discussed, and future development directions are also proposed.

Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses.

BACKGROUND: Global cyclical outbreaks of human enterovirus infections has positioned human enterovirus A71 (EV-A71) as a neurotropic virus of clinical importance. However, there remains a scarcity of internationally approved antivirals and vaccines. METHODS: In pursuit of repurposing drugs for combating human enteroviruses, we employed a comprehensive pharmacophore- and molecular docking-based virtual screen targeting EV-A71 capsid protein VP1-4, 3C protease, and 3D polymerase proteins. Among 15 shortlisted ligand candidates, we dissected the inhibitory mechanism of Tanomastat in cell-based studies and evaluated its in vivo efficacy in an EV-A71-infected murine model. FINDINGS: We demonstrated that Tanomastat exerts dose-dependent inhibition on EV-A71 replication, with comparable efficacy profiles in enterovirus species A, B, C, and D in vitro. Time-course studies suggested that Tanomastat predominantly disrupts early process(es) of the EV-A71 replication cycle. Mechanistically, live virus particle tracking and docking predictions revealed that Tanomastat specifically impedes viral capsid dissociation, potentially via VP1 hydrophobic pocket binding. Bypassing its inhibition on entry stages, we utilized EV-A71 replication-competent, 3Dpol replication-defective, and bicistronic IRES reporter replicons to show that Tanomastat also inhibits viral RNA replication, but not viral IRES translation. We further showed that orally administered Tanomastat achieved 85% protective therapeutic effect and alleviated clinical symptoms in EV-A71-infected neonatal mice. INTERPRETATION: Our study establishes Tanomastat as a broad-spectrum anti-enterovirus candidate with promising pre-clinical efficacy, warranting further testing for potential therapeutic application. FUNDING: MOE Tier 2 grants (MOE-T2EP30221-0005, R571-000-068-592, R571-000-076-515, R571-000-074-733) and A∗STARBiomedical Research Council (BMRC).

Glaucoma: Current and New Therapeutic Approaches.

Glaucoma is identified by the loss of retinal ganglion cells (RGCs). The primary approach to managing glaucoma is to control intraocular pressure (IOP). Lately, there has been an increasing focus on neuroprotective therapies for glaucoma because of the limited effectiveness of standard methods in reducing IOP and preventing ongoing vision deterioration in certain glaucoma patients. Various drug-based techniques with neuroprotective properties have demonstrated the ability to decrease the mortality of retinal ganglion cells. This study will analyze the currently recommended drug-based techniques for neuroprotection in the prospective treatment of glaucoma.

Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial.

INTRODUCTION: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU). METHODS: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth. RESULTS: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia. CONCLUSION: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Treatment effect of ultra-pulse dynamic CO2 laser and comedone extractor in dense comedones: a prospective, randomized, split-face, evaluator-blind, controlled clinical trial.

Clearance of comedone is challenging in the treatment of acne, as it is very likely to develop into inflammatory lesions. However, there is lack of effective treatments for dense comedones. Comedone extractor has been widely employed by dermatologists, but the effect is temporary and may cause irritation. CO2 laser is a potential method for dense comedones, but the efficacy and safety need to be explored. In this single-center, randomized, single-blind, self-controlled study, the faces of patients with dense comedones were randomly assigned into two sides receiving either ultra-pulse dynamic CO2 laser or comedone extraction at an interval of 2 weeks for 4 sessions. After 4 treatments, the average comedone reduction rate of the CO2 laser was 64.49%, which was higher than that by the extractor (46.36%) (P < .001). 79.16% of the patients reached over 50% reduction by CO2 laser, while only 37.5% on extractor treated side reached 50% clearance. Texture index, porphyrin index, red zone, erythema index, and transepidermal water loss decreased after both treatments, and CO2 laser showed more improvement. There was no difference in hydration index and melanin index between the two treatments. No permanent or severe side effects were observed on both sides. The CO2 laser showed higher comedone clearance with lower pain scores than the comedone extractor.

COVID-19 vaccine uptake in a predominantly minoritized cohort hospitalized during the early pandemic in New York City.

BACKGROUND: Minoritized communities in the United States have had higher COVID-19 mortality and lower vaccine uptake. The influence of previous SARS-CoV-2 infection, initial disease severity, and persistent symptoms on COVID-19 vaccine uptake in Black and Latinx communities has not been examined. OBJECTIVE: To investigate whether initial COVID-19 severity, persistent symptoms, and other correlates affected vaccine uptake in a predominantly minoritized cohort hospitalized for COVID-19 during the early pandemic in New York City. DESIGN: In this historical cohort study, we abstracted electronic health record data on demographics, comorbidities, hospital oxygen requirements, symptoms at 3 and 6 months post-admission, COVID-19 vaccinations through November 2022, and influenza vaccinations during the 2018-2019 through 2021-2022 seasons. Unadjusted and adjusted odds ratios were estimated through logistic regression analyses of correlates of COVID-19 vaccination, on-time vaccination, and boosting. PARTICIPANTS: Survivors among the first 1186 adult patients hospitalized for COVID-19 between March 1 and April 8, 2020 at a large quaternary care medical center in Northern Manhattan. MAIN MEASURES: Uptake of at least one COVID-19 vaccine dose, uptake of at least one booster, and on-time vaccination. KEY RESULTS: The 890 surviving individuals were predominantly Latinx (54%) and Non-Hispanic Black (15%). Most had one or more comorbidities (67%), and received at least one COVID-19 vaccine dose (78%). Among those vaccinated, 57% received at least one booster, and 31% delayed vaccination. 67% experienced persistent symptoms. Multiple logistic regression showed no association between vaccine uptake and disease severity or symptom persistence. However, older age and influenza vaccination during the COVID-19 era were associated with increased vaccination, booster uptake, and on-time vaccination. CONCLUSIONS: Pinpointing drivers of vaccine uptake and hesitancy is critical to increasing and sustaining COVID-19 vaccination as the field transitions to annual boosters. The association between influenza vaccination and increased vaccine uptake suggests that bundling vaccines for adults may be an effective delivery strategy.

Single incision mini sling for the treatment of urodynamic stress incontinence: Surgical outcomes and preoperative predictors of failure.

OBJECTIVE: To evaluate the surgical outcomes and predictors of failure of Single Incision Mini Sling (Ophira) in women with urodynamic stress incontinence. MATERIALS AND METHODS: Records of 115 women underwent anti-incontinence procedure using Ophira Mini Sling from June 2019 to September 2020 reviewed. Subjective evaluation was assessed using validated IIQ-7, UDI-6, POPDI-6 and PISQ-12 questionnaires. Multichannel urodynamics, 1-h pad test and 72-h voiding diary was performed as objective evaluation. Primary outcome was the objective cure rate of negative urine leak on provocative filling cystometry and 1-h pad test weight <2 g, and subjective cure rate was negative response to question 3 of UDI-6. Secondary outcome was to identify risk factors associated with failure for Ophira. RESULTS: Total of 108 women were evaluated. The objective cure rate was 91.7% with subjective cure rate of 86.1%. Comparison of clinical outcome shows significant improvement of USI post-operatively (p < 0.001) and reflected in 1-h pad test (p < 0.001). Improvement in all subjective evaluation parameters is seen except for POPDI-6. Failure of Ophira correlate significantly in women age >66 years, presence of asthma, pre-operative Intrinsic Sphincter Deficiency (ISD), and Maximum Urethral Closure Pressure (MUCP) value < 40 cmH20. CONCLUSION: Ophira Single Incision Mini Sling is safe and effective treatment option for USI, showing high objective and subjective cure rates with low incidence of complications. Non-modifiable risks of age ≥66 years, asthma status, pre-operative intrinsic sphincteric deficiency and low maximal urethral closure pressure were the factors of failure for Ophira.

Programmable editing of primary MicroRNA switches stem cell differentiation and improves tissue regeneration.

Programmable RNA editing is harnessed for modifying mRNA. Besides mRNA, miRNA also regulates numerous biological activities, but current RNA editors have yet to be exploited for miRNA manipulation. To engineer primary miRNA (pri-miRNA), the miRNA precursor, we present a customizable editor REPRESS (RNA Editing of Pri-miRNA for Efficient Suppression of miRNA) and characterize critical parameters. The optimized REPRESS is distinct from other mRNA editing tools in design rationale, hence enabling editing of pri-miRNAs that are not editable by other RNA editing systems. We edit various pri-miRNAs in different cells including adipose-derived stem cells (ASCs), hence attenuating mature miRNA levels without disturbing host gene expression. We further develop an improved REPRESS (iREPRESS) that enhances and prolongs pri-miR-21 editing for at least 10 days, with minimal perturbation of transcriptome and miRNAome. iREPRESS reprograms ASCs differentiation, promotes in vitro cartilage formation and augments calvarial bone regeneration in rats, thus implicating its potentials for engineering miRNA and applications such as stem cell reprogramming and tissue regeneration.

Bimetallic Sulfur-Doped Nickel-Cobalt Selenides as Efficient Bifunctional Electrocatalysts for the Complete Decomposition of Water.

The creation and enhancement of non-precious metal bifunctional catalysts with superior stability and stabilizing activity is necessary to achieve water splitting in alkaline media. The paper presents a method for preparing nickel-cobalt bimetallic selenides (NiCo-Sex/CF) using a combination of hydrothermal and high-temperature selenization techniques. NiCo-Sex/CF shows great potential as a catalyst for water separation. The catalyst's electronic structure and active centre can be modified by double doping with sulfur and selenium, resulting in increased selectivity and activity under varying reaction conditions. This method also offers the benefits of a simple preparation process and applicability to a wide range of catalytic reactions. Experimental results demonstrate that an overpotential of 194 mV produces a current density of 10 mA cm-2 when using this electrocatalyst as an OER catalyst. When used as a HER catalyst, the electrocatalyst required an overpotential of only 76 mV to generate a current density of 10 mA cm-2.Furthermore, a voltage of 1.5 V can drive the overall decomposition of water to achieve a current density of 10 mA cm-2. This study highlights the potential of sulfur-selenide double-doped catalysts for both scientific research and practical applications.

Ti-Substituted O3-NaNi0.5Mn0.3Ti0.2O2 Material with a Disordered Transition Metal Layer and a Stable Structure.

O3-type NaNi0.5Mn0.5O2 (NNM) is very competitive for sodium-ion batteries (SIBs) due to its high capacity and easy production. Nevertheless, the intricate phase transitions during the charging-discharging significantly impede its practical application. This paper proposes a strategy for successfully synthesizing NaNi0.5Mn0.3Ti0.2O2 (NNMT) by combining coprecipitation and a high-temperature solid-state method. This method introduces Ti elements while retaining the electrochemically active Ni2+ content, thus, the NNMT has a high initial specific capacity of 151.4 mAh g-1 at 1 C. It is demonstrated that introducing Ti4+ leads to the transition metal layers becoming disordered by ex situ XRD, thus mitigating the irreversible phase transition of the material. In addition, Ti4+ does not have an outer electron, which can reduce electron delocalization in the transition metal layer and improve the material's cyclic stability. The NNMT possesses a capacity retention rate of 60.66% after 150 cycles, much higher than the initial NNM's 18.96%. It also exhibits an excellent discharge capacity of 86.8 mAh g-1 at 5 C. In conclusion, the cycling and rate performance of the Ti-substituted NNMT are greatly improved without capacity loss, which offers innovative concepts for the modification means of the SIBs layered oxide cathode materials.

Benzaldehyde stimulates autophagy via the sonic hedgehog signaling pathway in mouse brain astrocytes after treatment with Angiostrongylus cantonensis excretory-secretory products.

Autophagy is a vital cellular process responsible for digesting various cytoplasmic organelles. This process plays a crucial role in maintaining cell survival and homeostasis, especially under conditions that cause nutrient deficiency, cellular damage, and oxidative stress. Neuroangiostrongyliasis is an infection caused by the parasitic nematode Angiostrongylus cantonensis and is considered as an emerging disease in many parts of the world. However, effective therapeutic strategies for neuroangiostrongyliasis still need to be further developed. In this study, we investigated the effects of benzaldehyde treatment on autophagy and sonic hedgehog (Shh) signaling in A. cantonensis-infected mice and its mechanisms. First, we found autophagosome generation in the central nervous system after A. cantonensis infection. Next, benzaldehyde combined with albendazole treatment reduced eosinophilic meningitis and upregulated the expression of Shh signaling- and autophagy-related molecules in A. cantonensis-infected mouse brains. In vitro experiments demonstrated that benzaldehyde could induce autophagy via the Shh signaling pathway in A. cantonensis excretory-secretory products (ESPs)-treated mouse astrocytes. Finally, benzaldehyde treatment also decreased lipid droplet accumulation and increased cholesterol production by activating the Shh pathway after ESPs treatment. In conclusion, these findings suggested that benzaldehyde treatment could alleviate brain damage by stimulating autophagy generation through the Shh signaling pathway.

Production of γ-aminobutyric acid by immobilization of two Yarrowia lipolytica glutamate decarboxylases on electrospun nanofibrous membrane.

This study harnesses glutamate decarboxylase (GAD) from Yarrowia lipolytica to improve the biosynthesis of γ-aminobutyric acid (GABA), focusing on boosting the enzyme's catalytic efficiency and stability by immobilizing it on nanofibrous membranes. Through recombinant DNA techniques, two GAD genes, YlGAD1 and YlGAD2, were cloned from Yarrowia lipolytica and then expressed in Escherichia coli. Compared to their soluble forms, the immobilized enzymes exhibited significant improvements in thermal and pH stability and increased resistance to chemical denaturants. The immobilization notably enhanced substrate affinity, as evidenced by reduced Km values and increased kcat values, indicating heightened catalytic efficiency. Additionally, the immobilized YlGAD1 and YlGAD2 enzymes showed substantial reusability, maintaining 50% and 40% of their activity, respectively, after six consecutive cycles. These results underscore the feasibility of employing immobilized YlGAD enzymes for cost-effective and environmentally sustainable GABA production. This investigation not only affirms the utility of YlGADs in GABA synthesis but also underscores the advantages of enzyme immobilization in industrial settings, paving the way for scalable biotechnological processes.

Bridging the gap in cardiac mass diagnosis: Advanced imaging, genetic associations, and biomarkers.

In this editorial we comment on the article by Huffaker et al published in a recent issue of the World Journal of Clinical Cases. We focus on cardiac tumors linked to genetic syndromes and the differential diagnosis of cardiac masses. As cardiomyocytes lack the ability to actively divide, primary cardiac tumors are extremely rare across all ethnicities and age groups. Once they occur, these tumors are often associated with genetic mutations and, occasionally, genetic syndromes. This underscores the importance of considering genetic mutations and syndromes when encountering these cases. The more common growths in the heart are thrombi and vegetations, which can mimic tumors, further making the differential diagnosis challenging. Among the imaging techniques, contrast-enhanced cardiac magnetic resonance imaging has the highest sensitivity for differential diagnosis. To aid in the differential diagnosis of cardiac masses, especially thrombi, appropriate utilization of biomarkers (i.e. D-dimer level) may provide pivotal clinical implications. Employing a multidisciplinary approach that integrates personal history, epidemiological insights, imaging findings, genetic markers, and biomarkers is therefore critical in the diagnostic process of cardiac masses.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

Purpose: The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Methods: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Results: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. Conclusions: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

Robust discriminator of chiral molecules via a topological invariant.

We propose a scheme for chirality discrimination via a topological invariant. The physical model is based on a three-level subspace of a molecule. By modulating the components of the control field with proper frequencies, two different two-level effective Hamiltonians are derived for the left-handed and the right-handed molecules. We parameterize the effective Hamiltonians with two angles and demonstrate that a topological quantum phase transition can be induced by tuning the effective Rabi frequency if the molecule is right-handed. This phenomenon provides a method to discriminate the chirality of the molecule by measuring a topological invariant, i.e., the Chern number, of the parametric manifold. Since the Chern number is robust against perturbations to the system, the scheme is insensitive to the systematic errors of the control fields, the deviations of the modulation frequencies, and decoherence of the molecule. Therefore, the scheme may provide useful perspectives to construct a robust discriminator of chiral molecules.

Local Injection of Stem Cells Can Be a Potential Strategy to Improve Bladder Dysfunction after Outlet Obstruction in Rats.

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-ß1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFß-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.