Sustainable functional urethral reconstruction improves early urinary continence after robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To evaluate the impact of sustainable functional urethral reconstruction (SFUR) on early recovery of urinary continence (UC) after robot-assisted radical prostatectomy. PATIENTS AND METHODS: Overall, 96 patients with primary prostate cancer were randomised into the SFUR or standard group (n = 48 each). The primary outcome was the 1-month UC recovery. Secondary outcomes included short-term (≤3 months) UC recovery, urinary function, micturition-related bother, perioperative complications, and oncological outcomes. Kaplan-Meier curves and Cox proportional hazard models were used to assess the 3-month UC recovery. Generalised estimating equations were used to compare postoperative urinary function and micturition-related bother. RESULTS: The 1-month UC recovery rates, median 24-h pad weights, and median operative time in the SFUR and standard groups were 73% and 49% (P = 0.017), 0 and 47 g (P = 0.001), and 125 and 103 min (P = 0.025), respectively. The UC recovery rates in the SFUR vs standard groups were 53% vs 23% at 1 week (P = 0.003), 53% vs 32% at 2 weeks (P = 0.038), and 93% vs 77% at 3 months (P = 0.025). The median time to UC recovery in the SFUR and standard groups was 5 and 34 days, respectively (log-rank P = 0.006); multivariable Cox regression supported this result (hazard ratio 1.73, 95% confidence interval 1.08-2.79, P = 0.024). Similar results were observed when UC was defined as 0 pads/day. Urinary function (P = 0.2) and micturition-related bother (P = 0.8) were similar at all follow-up intervals. The perioperative complication rates, positive surgical margin rates, and 1-year biochemical recurrence-free survival were comparable between both groups (all P > 0.05). CONCLUSION: SFUR resulted in earlier UC recovery without compromising postoperative urinary function. Long-term validation and multicentre studies are required to confirm the results of this novel technique.

Head-to-head comparison of prostate-specific membrane antigen PET and multiparametric MRI in the diagnosis of pretreatment patients with prostate cancer: a meta-analysis.

OBJECTIVES: To compare prostate-specific membrane antigen (PSMA) PET with multiparametric MRI (mpMRI) in the diagnosis of pretreatment prostate cancer (PCa). METHODS: Pubmed, Embase, Medline, Web of Science, and Cochrane Library were searched for eligible studies published before June 22, 2022. We assessed risk of bias and applicability by using QUADAS-2 tool. Data synthesis was performed with Stata 17.0 software, using the "midas" and "meqrlogit" packages. RESULTS: We included 29 articles focusing on primary cancer detection, 18 articles about primary staging, and two articles containing them both. For PSMA PET versus mpMRI in primary PCa detection, sensitivities and specificities in the per-patient analysis were 0.90 and 0.84 (p<0.0001), and 0.66 and 0.60 (p <0.0001), and in the per-lesion analysis they were 0.79 and 0.78 (p <0.0001), and 0.84 and 0.82 (p <0.0001). For the per-patient analysis of PSMA PET versus mpMRI in primary staging, sensitivities and specificities in extracapsular extension detection were 0.59 and 0.66 (p =0.005), and 0.79 and 0.76 (p =0.0074), and in seminal vesicle infiltration (SVI) detection they were 0.51 and 0.60 (p =0.0008), and 0.93 and 0.96 (p =0.0092). For PSMA PET versus mpMRI in lymph node metastasis (LNM) detection, sensitivities and specificities in the per-patient analysis were 0.68 and 0.46 (p <0.0001), and 0.91 and 0.90 (p =0.81), and in the per-lesion analysis they were 0.67 and 0.36 (p <0.0001), and 0.99 and 0.99 (p =0.18). CONCLUSION: PSMA PET has higher diagnostic value than mpMRI in the detection of primary PCa. Regarding the primary staging, mpMRI has potential advantages in SVI detection, while PSMA PET has relative advantages in LNM detection. CLINICAL RELEVANCE STATEMENT: The integration of prostate-specific membrane antigen (PSMA) PET into the diagnostic pathway may be helpful for improving the accuracy of prostate cancer detection. However, further studies are needed to address the cost implications and evaluate its utility in specific patient populations or clinical scenarios. Moreover, we recommend the combination of PSMA PET and mpMRI for cancer staging. KEY POINTS: • Prostate-specific membrane antigen PET has higher sensitivity and specificity for primary tumor detection in prostate cancer compared to multiparametric MRI. • Prostate-specific membrane antigen PET also has significantly better sensitivity and specificity for lymph node metastases of prostate cancer compared to multiparametric MRI. • Multiparametric MRI has better accuracy for extracapsular extension and seminal vesicle infiltration compared to ate-specific membrane antigen PET.

Advances in landscape and related therapeutic targets of the prostate tumor microenvironment.

The distinct tumor microenvironment (TME) of prostate cancer (PCa), which promotes tumor proliferation and progression, consists of various stromal cells, immune cells, and a dense extracellular matrix (ECM). The understanding of the prostate TME extends to tertiary lymphoid structures (TLSs) and metastasis niches to provide a more concise comprehension of tumor metastasis. These constituents collectively structure the hallmarks of the pro-tumor TME, including immunosuppressive, acidic, and hypoxic niches, neuronal innervation, and metabolic rewiring. In combination with the knowledge of the tumor microenvironment and the advancement of emerging therapeutic technologies, several therapeutic strategies have been developed, and some of them have been tested in clinical trials. This review elaborates on PCa TME components, summarizes various TME-targeted therapies, and provides insights into PCa carcinogenesis, progression, and therapeutic strategies.

Super-veil nerve-sparing extraperitoneal pure single-port robotic-assisted radical prostatectomy on da Vinci Si robotic system.

OBJECTIVES: To investigate the safety profile and short-term outcome of super-veil nerve-sparing extraperitoneal single-port robotic-assisted radical prostatectomy (espRARP) on da Vinci Si platform. METHODS: From December 2018 to March 2021, 106 consecutive patients with treatment-naive prostate cancer were prospectively included. espRARP was performed on da Vinci Si surgical platform. Operative time, estimated blood loss, Clavien-Dindo complication classification, continence, potency recovery, quality-of-life scores, and postoperative prostate-specific antigen (PSA) were documented. RESULTS: Patients aged 52-79 years (mean ± SD, 64.8 ± 6.15 yrs), with a median PSA of 9.2 ng/ml (IQR: 6.70, 16.83) and median prostate volume of 31.9 ml (IQR: 30.01, 38.54). 95.28% (101/106) were clinically localized. All patients underwent espRARP successfully with no open conversions. Operative time was 94.2 ± 30.26 min with an estimated blood loss of 68.5 ml (range, 50-120 ml). No Grade III complications or above were documented. Positive surgical margin was 17.9% (19/106). Median pain score at discharge was 0 (IQR: 0, 1.75) without use of opioid narcotics. Postoperative length of stay was 3 days (IQR: 1, 3), in which 28 patients were discharged within 24 h. Instant, 1-, 3-, and 6 month continence recovery was 18.9, 45.3, 79.2, 93.4, and 96.4%, respectively. Of the 43 patients who received nerve-sparing procedures, 13 (30.23%) resumed potency 6 months postoperatively. 12 month biochemical recurrence-free survival was 92.77% (77/83). CONCLUSIONS: Extraperitoneal single-port robotic-assisted radical prostatectomy is a safe and feasible technique. Combined with super-veil nerve-sparing procedures, it may provide satisfactory outcome in short-term functional recovery.

Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

BACKGROUND: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. METHODS: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. DISCUSSION: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

Modulation of high-energy γ-rays by collision of an ultra-high-energy electron with a tightly focused circularly polarized laser pulse.

Using an ultra-high-energy (γ⩾1000) electron to collide with laser pulses to generate high-energy γ-rays is an important way to treat cancer. We investigate a method for modulating high-energy γ-rays with higher energy and more collimation using tightly focused circularly polarized laser pulses colliding with an ultra-high-energy electron. Theoretical derivation and numerical simulation within the framework of classical electrodynamics show that higher electron initial energy, stronger laser intensity, and a longer pulse can generate higher γ-ray energy. The high-energy γ-rays generated by an electron with higher initial energies are more collimated. The increase of the laser intensity and the increase of the pulse width will increase the angular range of the high-energy γ-rays. At the same time, the phenomenon of the "jumping point," in which the radiation energy varies with the laser intensity, was found. Our findings have important implications for modulating better high-energy γ-ray sources.

A WeChat-based competency and performance checklist in basic surgical skills course for military medical academy undergraduates.

BACKGROUND: Basic surgical skills (BSS) is a key bridging course for medical students to acquire basic surgical maneuvers and practice animal surgery before clinical rotation, but the complexity of operational procedures and high demands on asepsis may lead to poor performance and frequent error during practice. The current study intended to improve BSS teaching outcomes by implementing smartphone app-based competency and performance checklists for medical academy undergraduates. METHODS: WeChat-based checklists containing competency and performance modules were designed, distributed and collected via smartphone. One hundred seventy-six third-grade undergraduate cadets majoring in clinical medicine or anesthesiology were prospectively enrolled, with 92 set as study group and 84 as control group. Checklists were distributed for self-evaluation before and after each class throughout the semester of autumn 2021-2022. Student age, previous Grade Point Average (GPA), average grades of BSS (including grade-A rate and pass rate), operative time, error rate, and perioperative complications of intestinal anastomosis performed on Beagle dogs between the groups were compared to evaluate the efficacy of the checklists. RESULTS: The students aged 20.2 ± 0.63 in Group A and 20.3 ± 0.92 in Group B (P = 0.15), with a previous GPA of 2.9 ± 0.61 vs. 2.87 ± 0.58 (P = 0.61). The average operative time on their final lesson of intestinal anastomosis was 192.3 ± 27.18 min vs. 213.8 ± 29.48 min (P < 0.001). All students passed in BSS course, with a final grade of 89.45 ± 4.360 in Group A and 86.64 ± 4.026 in Group B (P < 0.001), in which grade-A rate was 46.7% vs. 26.2% (P = 0.005). For perioperative comorbidities, 4/23 (17.4%) animals in Group A and 5/21 (23.8%) in Group B recorded wound dehiscence or other incision-related complications; no animals died in Group A, and 2 died in Group B due to hemorrhagic shock or sepsis. CONCLUSIONS: The implementation of WeChat-based checklist is a reflection of improved quality of teaching in BSS course that may promote the students' competency and performance.

Novel Long Non-coding RNA lncAMPC Promotes Metastasis and Immunosuppression in Prostate Cancer by Stimulating LIF/LIFR Expression.

Long non-coding RNAs (lncRNAs) participate in the development and progression of prostate cancer (PCa). We aimd to identify a novel lncRNA, named lncRNA activated in metastatic PCa (lncAMPC), and investigate its mechanisms and clinical significance in PCa. First, the biological capacity of lncAMPC in PCa was demonstrated both in vitro and in vivo. The lncAMPC was overexpressed in tumor tissue and urine of metastatic PCa patients and promoted PCa tumorigenesis and metastasis. Then, a mechanism study was conducted to determine how the lncAMPC-activated pathway contributed to PCa metastasis and immunosuppression. In the cytoplasm, lncAMPC upregulated LIF expression by sponging miR-637 and inhibiting its activity. In the nucleus, lncAMPC enhanced LIFR transcription by decoying histone H1.2 away from the upstream sequence of the LIFR gene. The lncAMPC-activated LIF/LIFR expressions stimulated the Jak1-STAT3 pathway to simultaneously maintain programmed death-ligand 1 (PD-L1) protein stability and promote metastasis-associated gene expression. Finally, the prognostic value of the expression of lncAMPC and its downstream genes in PCa patients was evaluated. High LIF/LIFR levels indicated shorter biochemical recurrence-free survival among patients who underwent radical prostatectomy. Therefore, the lncAMPC/LIF/LIFR axis plays a critical role in PCa metastasis and immunosuppression and may serve as a prognostic biomarker and potential therapeutic target.

Robotic Perineal Radical Prostatectomy: Initial Experience with the da Vinci Si Robotic System.

PURPOSE: To investigate the feasibility and surgical technique of robotic perineal radical prostatectomy (RPRP). MATERIALS AND METHODS: We retrospectively analyzed 6 consecutive patients diagnosed with prostate cancer from December 2018 to May 2019 who underwent RPRP at our center. Perioperative outcomes were recorded for safety and feasibility analysis. RESULTS: Six patients successfully underwent RPRP with no conversion to open procedures. Operative time was 140 (interquartile range [IQR] 123.75-148.75) min, console time was 70 (IQR 62.5-70) min, with an estimated blood loss of 125 (IQR 100-187.5) mL. Patients were discharged 2 days postoperatively (IQR range 1-3) with pelvic drainages removed. The Foley catheter was removed 2 weeks after surgery. Postoperative pathology revealed 5 patients with locally advanced disease (apical margin-positive prostate cancer [pT3a]bNx). Two patients had a positive surgical margin (33.3%). No complications of Clavien grade 3 and above were recorded; 1 patient had a delay in wound-healing of 1 week. Postoperative continence was achieved for 2 patients immediately after Foley catheter removal, 2 recovered 1-month postoperatively, and 1 recovered within 3 months, and 1 still had mild incontinence at the latest follow-up 1-month postoperatively. CONCLUSION: RPRP is a safe and feasible alternative for the transperitoneal route in selected patients. Further investigation is required to assess its oncological and quality-of-life results.

Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM.

Iminosugar C-glycoside analogues of α-D-GlcNAc-1-phosphate: synthesis and bacterial transglycosylase inhibition.

We herein describe the first synthesis of iminosugar C-glycosides of α-D-GlcNAc-1-phosphate in 10 steps starting from unprotected D-GlcNAc. A diastereoselective intramolecular iodoamination-cyclization as the key step was employed to construct the central piperidine ring of the iminosugar and the C-glycosidic structure of α-D-GlcNAc. Finally, the iminosugar phosphonate and its elongated phosphate analogue were accessed. These phosphorus-containing iminosugars were coupled efficiently with lipophilic monophosphates to give lipid-linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent inhibitory properties toward bacterial transglycosylases (TGase).

Role of long non-coding RNA TCONS_02443383 in regulating cell adhesion and peroxisome proliferator-activated receptor (PPAR) signaling genes in atherosclerosis: A New Zealand white rabbit model study.

OBJECTIVE: In this study, we performed RNA sequencing (RNA-seq) on the abdominal aorta tissue of New Zealand rabbits and investigated the potential association of lncRNA TCONS_02443383 with the development of AS through bioinformatics analysis of the sequencing data. The obtained results were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). METHOD: We induced an AS model in New Zealand rabbits by causing balloon injury to the abdominal aorta vascular wall and administering a high-fat diet. We then upregulated the expression level of the lncRNA TCONS_02443383 by injecting lentiviral plasmids through the ear vein. RNA sequencing (RNA-seq) was performed on the abdominal aorta tissues. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) analyses. RESULT: The overexpression of the lncRNA TCONS_02443383 led to an upregulation of peroxisome proliferator-activated receptor (PPAR) signaling pathways as well as genes related to cell adhesion. CONCLUSION: The overexpression of the lncRNA TCONS_02443383 can inhibit the occurrence and development of AS by upregulating peroxisome proliferator-activated receptor (PPAR) signaling pathways and genes related to cell adhesion.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases.

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

Value of Antibody Drug Conjugates for Gynecological Cancers: A Modern Appraisal Following Recent FDA Approvals.

Antibody drug conjugates (ADCs) are a new class of targeted anti-cancer therapies that combine a monoclonal tumor surface receptor-targeting antibody with a highly cytotoxic molecule payload. They enable delivery of cytotoxic therapy more directly to tumor cells and minimize delivery to healthy tissues. This review summarizes the existing literature about ADC therapies approved for use in gynecologic malignancies, relevant preclinical studies, as well as ongoing clinical trials.

Pembrolizumab with chemotherapy, with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer.

INTRODUCTION: Despite progress on prevention and treatment of cervical cancer, global morbidity and mortality remain high. Immunotherapy, in conjunction with standard chemotherapy, presents an opportunity for further benefit. AREAS COVERED: Here we report the pharmacologic properties, evidence for clinical efficacy, safety, and tolerability of pembrolizumab in addition to standard chemotherapy with and without bevacizumab for treatment of advanced or recurrent cervical cancer. EXPERT OPINION: In patients with progressive, recurrent, or metastatic PD-L1 expressing cervical cancer, without contraindication to anti-VEGF therapy, the use of pembrolizumab with bevacizumab and standard chemotherapy with carboplatin and paclitaxel is warranted. There is no evidence to support the use of pembrolizumab for this population broadly, and no evidence to support its use in PD-L1 non-expressing tumors.

Recent advances in single-site/incision robotic-assisted radical prostatectomy.

INTRODUCTION: Single-site robotic-assisted radical prostatectomy (ssRARP) has been successfully applied to treat prostate cancer. This review aims to describe the recent advances of surgical approaches, working accesses and novel robotic platforms in ssRARP. MATERIAL AND METHODS: A systematic literature search was performed by searching the PubMed, EMBASE, Web of Science and Scopus databases in December 2022 to identify all literature related to ssRARP. RESULTS: A total of 48 relevant studies were found worldwide from 2008 to 2023. Since the introduction of ssRARP, various modifications of this technique in surgical approaches, working accesses and novel robotic platforms have been developed. The application of ssRARP using the da Vinci SP platform has shown great superiority with encouraging clinical outcomes. DISCUSSION: There has been a potential shift toward ssRARP using the da Vinci SP platform due to its potential advantages in terms of lower blood loss, minimal postoperative pain, better cosmetic outcome and rapid recovery. More convincing evidence, further technical improvement and higher cost-effectiveness are needed for its widespread acceptance.

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial.

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

Targeting the JAK2-STAT3 pathway to inhibit cGAS-STING activation improves neuronal senescence after ischemic stroke.

Neuroinflammation after cerebral ischemia is a key event in progressive brain injury after ischemic stroke. The JAK2/STAT3 pathway is pivotal for neuroinflammation; however, its role in brain senescence after ischemic stroke is unclear. Here, we report that inflammation is increased in the brains of C57BL/6 stroke mice. Treatment of ischemic stroke in adult mice with a JAK kinase inhibitor (AG490) alleviated neurobehavioral defects, reduced brain infarct volume, reduced expression of pro-inflammatory cytokines, and decreased activation of pro-inflammatory microglia. Moreover, AG490 treatment reduced oxidative DNA damage and cellular senescence in the brains of mice following ischemic stroke. Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) were associated with inflammation and senescence. Furthermore, AG490 blocked cGAS/STING/NF-κBp65 expression. Overall, our results indicate that inhibition of JAK2/STAT3 can alleviate the negative neurological consequences of ischemic stroke, likely due to repression of cGAS/STING/NF-κB p65, leading to reduced neuroinflammation and neuronal senescence. Therefore, JAK2/STAT3 may represent a viable therapeutic target for preventing senescence after ischemic stroke.

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response.

BACKGROUND: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. OBJECTIVES: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. METHODS: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. RESULTS: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. CONCLUSIONS: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD.