Energetic cost of biosynthesis is a missing link between growth and longevity in mammals.

The comparative studies of aging have established a negative correlation between Gompertz postnatal growth constant and maximum lifespan across mammalian species, but the underlying physiological mechanism remains unclear. This study shows that the Gompertz growth constant can be decomposed into two energetic components, mass-specific metabolic rate and the energetic cost of biosynthesis, and that after controlling the former as a confounder, the negative correlation between growth constant and lifespan still exists due to a 100-fold variation in the latter, revealing that the energetic cost of biosynthesis is a link between growth and longevity in mammals. Previously, the energetic cost of biosynthesis has been thought to be a constant across species and therefore was not considered a contributor to the variation in any life history traits, such as growth and lifespan. This study employs a recently proposed model based on energy conservation to explain the physiological effect of the variation in this energetic cost on the aging process and illustrates its role in linking growth and lifespan. The conventional life history theory suggested a tradeoff between growth and somatic maintenance, but the findings in this study suggest that allocating more energy to biosynthesis may enhance the somatic maintenance and extend lifespan and, hence, reveal a more complex nature of the tradeoff.

Impact of age and anterior fibromuscular stroma preservation on post-enucleation voided volume.

PURPOSE: This study is centered on the critical role of anterior fibromuscular stroma (AFS) preservation in prostate enucleation, an emerging strategy aimed at minimizing postoperative urinary incontinence-a common concern in benign prostatic hyperplasia (BPH) surgeries. By focusing on postoperative voiding volumes (VV), our research investigates the efficacy of AFS preservation. This approach, distinct in its methodology, is hypothesized to improve urinary function post-surgery, thereby offering a potentially significant advancement in BPH surgical treatments. MATERIALS AND METHODS: A retrospective analysis was conducted, comparing patients who underwent prostate enucleation in 2017 without intentional AFS preservation to those in 2019 with this technique. We examined variables including age, BMI, diabetes, hypertension, and preoperative VV to assess their effect on post-catheter removal VV. The study's methodology includes a thorough review of the primary statistical analysis methods employed. RESULTS: Our analysis indicates that while the 2017 and 2019 cohorts were similar in most preoperative parameters, the 2019 group that underwent AFS-preserved surgery showed a significant improvement in postoperative VVs. This was less pronounced in the patient group aged over 70, underscoring the importance of this demographic in our study. CONCLUSIONS: The study concludes that intentional preservation of AFS during prostate enucleation positively impacts early postoperative VVs, with limited improvement in older patients. These findings highlight the potential of AFS preservation not only in enhancing urinary outcomes post-surgery but also in shaping future BPH surgical procedures and research directions.

Analysis of urinary retention after endoscopic prostate enucleation and its subsequent impact on surgical outcomes.

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.

FOXF2 oppositely regulates stemness in luminal and basal-like breast cancer cells through the Wnt/beta-catenin pathway.

The stemness of cancer cells contributes to tumorigenesis, the heterogeneity of malignancies, cancer metastasis, and therapeutic resistance. However, the roles and regulatory mechanisms maintaining stemness among breast cancer subtypes remain elusive. Our previous studies have demonstrated that ectopic expression and dynamic alteration of the mesenchymal transcription factor forkhead box F2 (FOXF2) differentially regulates breast cancer progression and metastasis organotropism in a cell subtype-specific manner. Here, we reveal the underlying mechanism by which FOXF2 enhances stemness in luminal breast cancer cells but suppresses that in basal-like breast cancer (BLBC) cells. We show that luminal breast cancer and BLBC cells with FOXF2-regulated stemness exhibit partial mesenchymal stem cell properties that toward osteogenic differentiation and myogenic differentiation, respectively. Furthermore, we show that FOXF2 activates the Wnt signaling pathway in luminal breast cancer cells but represses this pathway in BLBC cells by recruiting nuclear receptor coactivator 3 (NCoA3) and nuclear receptor corepressor 1 (NCoR1) to the promoters of Wnt family member 2B (WNT2B) and frizzled class receptor 1 (FZD1) genes to activate and repress their transcription, respectively. We propose that targeting the Wnt signaling pathway is a promising strategy for the treatment of breast cancers with dysregulated expression of FOXF2.

Full-field hard X-ray nano-tomography at SSRF.

An in-house designed transmission X-ray microscopy (TXM) instrument has been developed and commissioned at beamline BL18B of the Shanghai Synchrotron Radiation Facility (SSRF). BL18B is a hard (5-14 keV) X-ray bending-magnet beamline recently built with sub-20 nm spatial resolution in TXM. There are two kinds of resolution mode: one based on using a high-resolution-based scintillator-lens-coupled camera, and the other on using a medium-resolution-based X-ray sCMOS camera. Here, a demonstration of full-field hard X-ray nano-tomography for high-Z material samples (e.g. Au particles, battery particles) and low-Z material samples (e.g. SiO2 powders) is presented for both resolution modes. Sub-50 nm to 100 nm resolution in three dimensions (3D) has been achieved. These results represent the ability of 3D non-destructive characterization with nano-scale spatial resolution for scientific applications in many research fields.

Genome-wide identification and functional characterization of borneol dehydrogenases in Wurfbainia villosa.

MAIN CONCLUSION: Genome-wide screening of short-chain dehydrogenases/reductases (SDR) family reveals functional diversification of borneol dehydrogenase (BDH) in Wurfbainia villosa. Wurfbainia villosa is an important medicinal plant, the fruits of which accumulate abundant terpenoids, especially bornane-type including borneol and camphor. The borneol dehydrogenase (BDH) responsible for the conversion of borneol to camphor in W. villosa remains unknown. BDH is one member of short-chain dehydrogenases/reductases (SDR) family. Here, a total of 115 classical WvSDR genes were identified through genome-wide screening. These WvSDRs were unevenly distributed on different chromosomes. Seven candidate WvBDHs based on phylogenetic analysis and expression levels were selected for cloning. Of them, four BDHs can catalyze different configurations of borneol and other monoterpene alcohol substrates to generate the corresponding oxidized products. WvBDH1 and WvBDH2, preferred (+)-borneol to (-)-borneol, producing the predominant ( +)-camphor. WvBDH3 yielded approximate equivalent amount of (+)-camphor and (-)-camphor, in contrast, WvBDH4 generated exclusively (+)-camphor. The metabolic profiles of the seeds showed that the borneol and camphor present were in the dextrorotatory configuration. Enzyme kinetics and expression pattern in different tissues suggested WvBDH2 might be involved in the biosynthesis of camphor in W. villosa. All results will increase the understanding of functional diversity of BDHs.

Low-complexity LDPC decoding algorithms for ultra-high-order modulated signals.

Low-complexity decoding algorithms and ultra-high-order modulation formats are necessary to meet data rate requirements in excess of 1 Tbps. The information bottleneck algorithm has been effectively applied to the LDPC decoding algorithm in recent years, and its performance is comparable to that of the double-precision information propagation technique. However, the application of information bottleneck decoding algorithms in ultra-high order modulation forms has received little attention. Furthermore, the number of table lookups required for a single decoding loop is square to the node degree, which is undesirable for optical communications. We present a low-complexity LDPC decoding technique for ultra-high-order modulated signals in this study. First, the algorithm employs multivariate covariates to build an information bottleneck framework, which introduces the processing required for applying the information bottleneck algorithm to 1024-QAM signals and the requirement of combining higher-order modulation formats with LDPC codes. The technique makes use of a bidirectional recursive network and the symmetry of quantized information to reuse the same set of tables, considerably reducing the number of table lookup operations required in the decoding process. Constructing a coherent optical communication system with 1024-QAM signals proves that the proposed algorithm can operate effectively. The performance sacrifice of 0.2 ∼ 0.3 dB reduces the number of table lookup operations required for decoding from square to linear magnitude, which greatly reduces the decoding time required in optical communication.

Oblique illumination-induced transformation between the FP and the Fano resonances through an all-dielectric metasurface.

We demonstrate the angular dispersive transmission properties of electromagnetic fields with both the Fabry-Pérot (FP) resonances and Fano resonances through an all-dielectric metasurface consisting of a silicon bar array over the silicon dioxide slab. More specifically, when the normal incidence is casting over the metasurface, solely FP resonances will be achieved, and the silicon rod array can be equivalent to another dielectric combining with the silicon dioxide substrate. On the other hand, the Fano resonances will become dominant when the metasurface is under the wide-angular oblique illumination, raising the asymmetry in the silicon bar array to function as toroidal dipoles and electric quadrupoles and thus enable the proposed all-dielectric metasurface to achieve different resonances with the variation of different angular illuminations.

Exosome from adipose-derived mesenchymal stem cells attenuates scar formation through microRNA-181a/SIRT1 axis.

Pathological scarring is the greatest challenge after injury. Exosome from adipose-derived mesenchymal stem cells has been reported effective to improve hypertrophic scar. This study focused on the possible mechanisms during this process. Exosomes from adipose-derived mesenchymal stem cells were extracted first. Hypertrophic scar tissue and paired normal skin tissue were collected from patients. Mice skin incision model and fibroblasts model were established. TGF-ß1 was used to stimulate fibroblasts to myofibroblasts transdifferentiation. It was found that exosomes injection could decrease collagen sediment after wound healing. During which, the expression of microRNA-181a decreased. Further, we found that expression of microRNA-181a in scar tissue was higher than in normal skin. Then hypertrophic scar-derived fibroblasts were used for in vitro study. It was found that similar to the use of exosomes, microRNA-181a inhibitor decreased the expression of collagen and α-SMA. While microRNA-181a mimics suppressed the effects of exosomes. During fibroblast to myofibroblast trans-differentiation, level of microRNA-181a well as levels of scar-related molecules also decreased with the use of exosomes and vice versa. SIRT1 was confirmed one of the downstream targets of microRNA-181a. Suppression of SIRT1 led to diminished effects of exosomes in hypertrophic scar derived fibroblasts. In mice skin incision model, injection of SIRT1 inhibitor led to increased collagen synthesis. In conclusion, exosomes from Adipose-derived mesenchymal stem cells are promising to antagonize scarring through the regulation of microRNA-181a/SIRT1 axis.

METTL14 inhibits malignant progression of oral squamous cell carcinoma by targeting the autophagy-related gene RB1CC1 in an m6A-IGF2BP2-dependent manner.

N6-methyladenosine (m6A) plays crucial roles in tumorigenesis and autophagy. However, the underlying mechanisms mediated by m6A and autophagy in the malignant progression of oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we revealed that down-regulated expression of METTL14 was correlated with advanced clinicopathological characteristics and poor prognosis in OSCC. METTL14 knockdown significantly inhibited autophagy and facilitated malignant progression in vitro, and promoted tumor growth and metastasis in vivo. A cell model of rapamycin-induced autophagy was established to identify RB1CC1 as a potential target gene involved in m6A-regulated autophagy in OSCC, through RNA sequencing and methylated RNA immunoprecipitation sequencing (meRIP-seq) analysis. Mechanistically, we confirmed that METTL14 posttranscriptionally enhanced RB1CC1 expression in an m6A-IGF2BP2-dependent manner, thereby affecting autophagy and progression in OSCC, through methylated RNA immunoprecipitation qRT-PCR (meRIP-qPCR), RNA stability assays, mutagenesis assays and dual-luciferase reporter. Collectively, our findings demonstrated that METTL14 serves as an OSCC suppressor by regulating the autophagy-related gene RB1CC1 through m6A modification, which may provide a new insight for the diagnosis and therapy of OSCC.

Anterior fibromuscular stroma-preserved endoscopic enucleation of the prostate: a precision anatomical approach.

BACKGROUND: Benign prostate obstruction (BOO) is becoming increasingly important in this aging society. Some urge/stress urinary incontinence (UUI/SUI) still occurs after endoscopic enucleation of the prostate (EEP). It remains unclear how post-EEP incontinence can be avoided. Currently, early apical release to ameliorate the traction of the external sphincter is the best technique for incontinence prevention. OBJECTIVE: To describe our surgical technique of anterior fibromuscular stroma (AFS)-preserved EEP for BOO. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 60 consecutive patients who underwent AFS-preserved EEP for BOO in our center from September 2019 to December 2019 were retrospectively reviewed. SURGICAL PROCEDURE: AFS-preserved EEP starts at the 12 o'clock position of the urethra, and the junction between the AFS and transitional zone (T-zone) was identified. The AFS and T-zone were separated first to protect the AFS in the initial operative procedure. Then, following the usual enucleation procedure, AFS-preserved EEP could be achieved. MEASUREMENTS: Postoperative prostate-specific antigen (PSA), testosterone, urethral stricture, and voiding status, such as incontinence, uroflow, and postvoiding residual urine were assessed. RESULTS AND LIMITATIONS: The data show that AFS-preserved EEP could achieve similar surgical outcomes as other early apical release approaches. CONCLUSIONS: The preserved AFS provides a nice landmark at the 12 o'clock position during EEP.

Chronic Pain, Analgesics, and Cognitive Status: A Comprehensive Mendelian Randomization Study.

BACKGROUND: Observational studies have suggested an intricate relationship among chronic pain (CP), use of analgesics, and cognitive status, but it remains unclear whether these associations are of a causal nature. METHODS: To investigate the causal relationship among them, summary statistics of 9 types of CP (headache, hip, neck/shoulder, stomach/abdominal, back, knee, facial, general, and multisite CP), analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, salicylic acid and derivatives, and anilides), and cognitive status (cognitive function, Alzheimer's disease [AD], vascular dementia, Lewy body dementia [LBD], and dementia) were included in this Mendelian randomization (MR) study. As both CP and analgesic use were associated with cognitive status and vice versa, we performed a bidirectional MR analysis between CP or analgesics and dementia using strong genetic instruments ( P < .001) identified from genome-wide association studies (GWAS). The inverse-variance weighted method was applied to calculate estimates. The MR estimated odds ratio (OR) was interpreted as odds of outcome per unit increase in the exposure. The Benjamini-Hochberg method was applied to adjust the P value for multiple testing, and P < .05 means statistically significant. RESULTS: Multisite CP (MCP) was associated with worse cognitive function (OR [95% confidence interval], 0.69 [0.53-0.89], P = .043), but no significant reverse effect of cognitive status on CP was found. There were no significant associations observed between analgesics and cognitive status. Unexpectedly, patients with AD and LBD had significantly lower exposure to anilides (AD: OR = 0.97 [0.94-0.99], P = .034; LBD: OR = 0.97 [0.96-0.99], P = .012) and NSAIDs (AD: OR = 0.96 [0.93-0.98], P = .012; LBD: OR = 0.98 [0.96-0.99], P = .034). CONCLUSIONS: Our findings indicate that an elevated number of CP sites predict future cognitive decline. Patients with dementia had lower exposure to anilides and NSAIDs, suggesting that they might not be adequately medicated for pain.

Is mitochondrial reactive oxygen species production proportional to oxygen consumption? A theoretical consideration.

It has been assumed that at the whole organismal level, the mitochondrial reactive oxygen species (ROS) production is proportional to the oxygen consumption. Recently, a number of researchers have challenged this assumption, based on the observation that the ROS production per unit oxygen consumed in the resting state of mitochondrial respiration is much higher than that in the active state. Here, we develop a simple model to investigate the validity of the assumption and the challenge of it. The model highlights the significance of the time budget that mitochondria operate in the different respiration states. The model suggests that under three physiologically possible conditions, the difference in ROS production per unit oxygen consumed between the respiration states does not upset the proportionality between the whole animal ROS production and oxygen consumption. The model also shows that mitochondrial uncoupling generally enhances the proportionality.

FTO Sensitizes Oral Squamous Cell Carcinoma to Ferroptosis via Suppressing ACSL3 and GPX4.

Ferroptosis is a newly established form of regulated cell death characterized by intracellular lipid peroxidation and iron accumulation that may be a promising cancer treatment strategy. However, the function and therapeutic value of ferroptosis in oral squamous cell carcinoma (OSCC) remain inadequately understood. In the present study, we investigated the biological role of the fat mass and obesity-associated gene (FTO) in ferroptosis in the context of OSCC. We found that OSCC had greater potential for ferroptosis, and FTO is associated with ferroptosis. Furthermore, higher FTO expression sensitized OSCC cells to ferroptosis in vitro and in vivo. Mechanistically, FTO suppressed the expression of anti-ferroptotic factors, acyl-CoA synthetase long-chain family member 3 (ACSL3) and glutathione peroxidase 4 (GPX4), by demethylating the m6A modification on the mRNA of ACSL3 and GPX4 and decreasing their stability. Taken together, our findings revealed that FTO promotes ferroptosis through ACSL3 and GPX4 regulation. Thus, ferroptosis activation in OSCC with high FTO levels may serve as a potential therapeutic target.

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells.

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Lifestyle and Diet as Risk Factors for Urinary Stone Formation: A Study in a Taiwanese Population.

Background and Objectives: Urinary tract stones have long been a common ailment afflicting the population, with a high incidence and a wide distribution across different age groups. Effectively preventing the occurrence of urinary tract stones is of paramount importance. The primary aim of this study is to investigate the correlations between individual characteristics, water consumption habits, dietary habits, exercise habits, and the occurrence of urinary tract stones in a Taiwanese population. Materials and Methods: This study is cross-sectional research conducted over one month in 2022. One hundred eligible urinary stone cases were recruited through physician screening at outpatient clinics, and an additional one hundred samples from surgical outpatients without urinary tract stones were included as the control group. A questionnaire survey was employed to gather information on demographic variables, dietary habits, water consumption, and exercise habits of the cases. Descriptive statistics, chi-square tests, and logistic regression were used to explore the impact of relevant factors on urinary stone formation. Results: The analysis results revealed that among the demographic variables, males exhibited a higher risk of contracting urinary tract stones than females, and the majority of cases fell within the 40- to 49-year-old age group. Unhealthy lifestyle habits such as smoking and betel nut chewing also demonstrated a higher susceptibility to urinary tract stones. A logistic regression analysis showed that individuals who engaged in physical activity more than three times per week and those with inadequate water intakes had a higher risk of developing urinary tract stones. Conclusions: There is a close relationship between lifestyle and urinary tract stones. It is recommended that individuals continue to hydrate adequately during exercise.

Comparative Analysis of Surgical Outcomes of Flexible Ureteroscopy and Da Vinci Robotic Surgery in Community Patients with Renal Pelvic Stones Larger than 2 cm.

Background and Objectives: This study evaluated and compared the surgical outcomes of retrograde intrarenal surgery (RIRS) lithotripsy versus robot-assisted laparoscopic pyelolithotomy (RAPL) in community patients with renal pelvic stones larger than 2 cm. Materials and Methods: A total of 77 patients who underwent RIRS (RIRS group, n = 50) or RAPL (RAPL group, n = 27) at our institution between December 2016 and July 2022 were recruited. A single surgeon performed all surgical operations. Preoperative, operative, and postoperative data were recorded. The study evaluated various clinical outcomes, namely, urinary tract infections, analgesic use, emergency room readmissions, stone clearance rates, surgical complications, and medical expenditures associated with the treatment courses, and compared them between the groups. Results: The RAPL group had a larger mean stone diameter and higher degree of hydronephrosis than the RIRS group did. The RIRS group had superior outcomes regarding operative time, length of postoperative hospital stay, surgical wound pain, and medical expenditures. Regarding postoperative outcomes, comparable rates of postoperative urinary tract infection, prolonged analgesic use, and emergency room readmissions were observed between the groups. However, the RAPL group had a higher stone clearance rate than the RIRS group did (81.5% vs. 52.0%, p = 0.014). Conclusions: For the surgical treatment of renal pelvis stones larger than 2 cm, RAPL has a superior stone clearance rate than RIRS; however, RIRS achieves superior outcomes in terms of medical expenditures, length of hospital stay, and surgical wound pain. Both procedures were equally safe.

A Compartmentalized Nanoreactor Formed by Interfacial Hydrogelation for Cascade Enzyme Catalytic Therapy.

Some cellular enzymatic pathways are located within a single organelle, while most others involve enzymes that are located within multiple compartmentalized cellular organelles to realize the efficient multi-step enzymatic process. Herein, bioinspired by enzyme-mediated biosynthesis and biochemical defense, a compartmented nanoreactor (Burr-NCs@GlSOD ) was constructed through a self-confined catalysis strategy with burr defect-engineered molybdenum disulfide/Prussian blue analogues (MoS2 /PBA) and an interfacial diffusion-controlled hydrogel network. The specific catalytic mechanism of the laccase-like superactivity induced hydrogelation and cascade enzyme catalytic therapy were explored. The confined hydrogelation strategy introduces a versatile means for nanointerface functionalization and provides insight into biological construction of simulated enzymes with comparable activity and also the specificity to natural enzymes.

Discovery of the ATPase Activity of a Cobalt-Type Nitrile Hydratase Activator and Its Promoting Effect on Enzyme Maturation.

An activator protein and a metal ion are two factors known to be indispensable for the maturation of nitrile hydratase (NHase). Here, the third key factor, adenosine triphosphate (ATP), was identified to play an important role in the activation of Co-type NHase. Free phosphate measurements revealed that the Co-type activator protein can hydrolyze ATP/GTP with appreciable performance and that such catalytic performance is related to NHase activity. Computational analysis and site-directed mutagenesis identified several potential hot spot residues involved in the binding of ATP to Co-type activator protein, and an E60A/W61A/D62A/I139A/T141A combinatorial variant reduced the ATPase activity to 18% of its original level. Further NHase activation studies using the combinatorial variant demonstrated that although the ATPase activity of the Co-type activator protein correlated with NHase activity, a low ATP concentration of 0.5 mmol/L was optimal for NHase activation, with higher ATP concentrations potentially inhibiting NHase activity.

Exosomal microRNA-23b-3p promotes tumor angiogenesis and metastasis by targeting PTEN in salivary adenoid cystic carcinoma.

MicroRNA (miR)-23b-3p is known to target various genes that are involved in cancer-related pathways. Exosomes are emerging intercellular communication agents. Exosomes secreted by cancer cells can deliver active molecules to the surrounding stromal cells, thereby influencing the recipient cells and promoting the development of cancers. However, the role of exosomal miR-23b-3p in salivary adenoid cystic carcinoma (SACC) is not yet clear. In this study, we set out to investigate the potential role of cancer-derived exosomal miR-23b-3p-related phosphatase and tensin homolog deleted on chromosome 10 in the alteration of angiogenesis and vascular permeability in SACC. We investigated the effect of exosomal miR-23b-3p on the progression of SACC. In vitro experiments indicated that exosomal miR-23b-3p led to an upregulation of vascular permeability, and reduced expression of tight junction proteins. In addition, exosomal miR-23b-3p also enhanced angiogenesis and migration. Next, the angiogenic effect of exosomal miR-23b-3p was validated in vivo, as it led to an increase in the tumor microvasculature. Furthermore, the growth rate of SACC was faster after injection of exosomes loaded with cholesterol-modified miR-23b-3p in mice. In conclusion, these results revealed that SACC cell-derived exosomes play an important role in promoting angiogenesis and local vascular microleakage of SACC by transporting miR-23b-3p, which suggests that miR-23b-3p in the exosomes may be a potential biomarker for distant metastasis of SACC. This suggests the potential of a novel therapeutic target by delivering anti-miR-23b-3p that focuses on exosomes.