Berberine enhances the function of intestinal stem cells in healthy and radiation-injured mice.

Intestinal stem cells (ISCs) are pivotal for the maintenance and regeneration of the intestinal epithelium. Berberine (BBR) exhibits diverse biological activities, but it remains unclear whether BBR can modulate ISCs' function. Therefore, we investigated the effects of BBR on ISCs in healthy and radiation-injured mice and explored the potential underlying mechanisms involved. The results showed that BBR significantly increased the length of the small intestines, the height of the villi, and the depth and density of the crypts, promoted the proliferation of cryptal epithelial cells and increased the number of OLFM4+ ISCs and goblet cells. Crypts from the BBR-treated mice were more capable of growing into enteroids than those from untreated mice. BBR alleviated WAI-induced intestinal injury. BBR suppressed the apoptosis of crypt epithelial cells, increased the quantity of goblet cells, and increased the quantity of OLFM4+ ISCs and tdTomato+ progenies of ISCs after 8 Gy WAI-induced injury. Mechanistically, BBR treatment caused a significant increase in the quantity of p-S6, p-STAT3 and p-ERK1/2 positive cryptal epithelial cells under physiological conditions and after WAI-induced injury. In conclusion, BBR is capable of enhancing the function of ISCs either physiologically or after radiation-induced injury, indicating that BBR has potential value in the treatment of radiation-induced intestinal injury.

Clinical Effect of Uterosacral and Cardinal Ligament Fixation versus Sacrospinous Ligament Fixation of Vaginal Vault Prolapse: A Retrospective Analysis.

Objective: This study aimed at comparing sacrospinous ligament fixation (SSLF) with uterosacral and cardinal ligament fixation (USCLF) concerning complications and outcomes in patients with pelvic organ prolapse (POP). Methods: A retrospective analysis was performed on the clinical data of patients with POP stage III or above uterine prolapse treated at Wenzhou People's Hospital from January 2013 to December 2019. Patients were divided into two groups: USCLF group and SSLF group. The perioperative indicators, postoperative complications, pelvic organ prolapse quantification (POP-Q), Pelvic Floor Distress Inventory-20 (PFDI-20), and POP/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) scores of the groups were analyzed and compared. Results: (1) The operative time and intraoperative blood loss in the USCLF group were lower than those in the SSLF group, with statistical significance (p < 0.05). (2) The incidence of postoperative buttock pain in the SSLF group was 10.7% (6/56), higher than that in the USCLF group (0/56) (Fisher's exact test, p = 0.027). (3) At one year of follow-up, significant improvement in Aa, Ba, C, Ap, and Bp values was observed in both groups (p < 0.05). The values of the Aa and Ba sites in the USCLF group were lower than those in the SSLF group one year after surgery (p < 0.05). (4) The PFDI-20 and PISQ-12 scores of the groups one year after surgery were lower than those before surgery (p < 0.05). Conclusion: Uterosacral and cardinal ligament suture fixation leads to less bleeding and better postoperative quality of life than preoperative and may be better than SSLF at preventing the recurrence of anterior wall prolapse after surgery.

Enhanced hair growth effects through low-level vortex beams radiation: An experimental animal study.

Photobiomodulation therapy (PBMT) is a non-invasive and pain-less treatment for hair loss. Researches on PBMT rarely considered the impact of different light structures. In this study, we irradiated shaven rats with both 650 nm, m = 32 vortex beams and ordinary Gaussian beams. The laser treatment was performed at 24-hour intervals for 20 days. The energy density was set to 4.25 J/cm2 . The results indicated that low-level vortex beam irradiation led to better stimulation of hair growth than the Gaussian beams, which might be related to deeper penetration. The underlying biological mechanisms are discussed in terms of the activation of Wnt/ß-catenin/sonic hedgehog pathway. Our results suggest that low-level vortex beam irradiation is advantageous to the treatment of hair loss because it is technically feasible, convenient and effective.

Berberine attenuates hyperalgesia in mice with adenomyosis.

PURPOSE: Adenomyosis is a common gynecological disease, but its pathogenesis and treatment options are not yet completely clear. This study aimed to investigate the analgesic effect of berberine on tamoxifen-induced neonatal mouse adenomyosis and its curative effects on the disease. METHODS: The mouse adenomyosis model was established in neonatal female mice via oral administration of tamoxifen suspended solution. Adenomyosis mice were given berberine by intraperitoneal injection with the dosage of 5, 10, and 20 mg/kg body weight, respectively, at 17 weeks after birth. The pain sensation of the mice was evaluated by hotplate and tail-flick tests. The mRNA levels of gene expression were detected by RT-qPCR. The protein expression was analyzed by ELISA and Western blot. RESULTS: Berberine reduced the uterine weight, suppressed the myometrial infiltration of ectopic endometrium, improved the hotplate and tail-flick latency of the adenomyosis mice. Mechanistically, berberine downregulated the expression of genes related to pain and inflammation, such as TRPV1, COX-2, VEGF and OTR, impaired the inflammatory response at the DRG site, and inhibited the expression of TLR4 in DRG and uterine tissues. CONCLUSIONS: Berberine attenuates hyperalgesia and exhibits analgesic and therapeutic effects on adenomyosis mice.

Improvement of Gold Nanorods in Photothermal Therapy: Recent Progress and Perspective.

Cancer is a life-threatening disease, and there is a significant need for novel technologies to treat cancer with an effective outcome and low toxicity. Photothermal therapy (PTT) is a noninvasive therapeutic tool that transports nanomaterials into tumors, absorbing light energy and converting it into heat, thus killing tumor cells. Gold nanorods (GNRs) have attracted widespread attention in recent years due to their unique optical and electronic properties and potential applications in biological imaging, molecular detection, and drug delivery, especially in the PTT of cancer and other diseases. This review summarizes the recent progress in the synthesis methods and surface functionalization of GNRs for PTT. The current major synthetic methods of GNRs and recently improved measures to reduce toxicity, increase yield, and control particle size and shape are first introduced, followed by various surface functionalization approaches to construct a controlled drug release system, increase cell uptake, and improve pharmacokinetics and tumor-targeting effect, thus enhancing the photothermal effect of killing the tumor. Finally, a brief outlook for the future development of GNRs modification and functionalization in PTT is proposed.

Advances and trends of hydrogel therapy platform in localized tumor treatment: A review.

Due to limitations of treatment and the stubbornness of infiltrative tumor cells, the outcome of conventional antitumor treatment is often compromised by a variety of factors, including severe side effects, unexpected recurrence, and massive tissue loss during the treatment. Hydrogel-based therapy is becoming a promising option of cancer treatment, because of its controllability, biocompatibility, high drug loading, prolonged drug release, and specific stimuli-sensitivity. Hydrogel-based therapy has good malleability and can reach some areas that cannot be easily touched by surgeons. Furthermore, hydrogel can be used not only as a carrier for tumor treatment agents, but also as a scaffold for tissue repair. In this review, we presented the latest researches in hydrogel applications of localized tumor therapy and highlighted the recent progress of hydrogel-based therapy in preventing postoperative tumor recurrence and improving tissue repair, thus proposing a new trend of hydrogel-based technology in localized tumor therapy. And this review aims to provide a novel reference and inspire thoughts for a more accurate and individualized cancer treatment.

All-trans retinoic acid reduces cancer stem cell-like cell-mediated resistance to gefitinib in NSCLC adenocarcinoma cells.

BACKGROUND: The enrichment of cancer stem cell-like cells (CSCs) has been considered to be responsible for tumor progression after an initial response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung adenocarcinoma (NSCLC/ADC). CSCs with ALDH1A1bright /CD44high expression contribute to the TKIs resistance in NSCLC/ADC cells. All-trans retinoic acid (ATRA) has been shown to be a potential targeted therapy against CSCs due to its ability to inhibit ALDH1A1 activity. We therefore investigated whether ATRA could circumvent the resistance to improve the response to gefitinib in NSCLC/ADC cells. METHODS: Treatment of NSCLC/ADC A549 and H1650 cells with gefitinib enriched the gefitinib surviving cells (GSCs). The expression of ALDH1A1 and CD44 and the IC50 values for gefitinib were determined by flow cytometry (FCM) and crystal violet assay in GSCs and ATRA-treated GSCs, respectively. Using DEAB as the positive control, direct inhibitory effect of ATRA on ALDH1A1 activity was determined by ALDEFLUOR assay, RESULTS: GSCs showed higher expression of ALDH1A1 and CD44 and IC50 values for gefitinib than their respective parental cells, suggesting that gefitinib can lead to propagation of CSC-enriched gefitinib-resistant cells. Treatment with ATRA was found to significantly reduce the increased expression of ALDH1A1 and CD44 and the IC50 values for gefitinib in A549GSC and H1650GSC cells, and ATRA could directly inhibit active ALDH1A1 as compared to DEAB. CONCLUSION: Our findings suggest that combination treatment with ATRA prevents gefitinib-induced enrichment of ALDH1A1bright/CD44high CSCs and enhances gefitinib-induced growth inhibition of NSCLC/ADC cells.

Intracranial Aneurysm Presenting Robust Metal Artifact.

BACKGROUND: Intracranial aneurysm (IA) is a debilitating cerebrovascular degeneration. Current clinical diagnosis relies mainly on conventional angiogram except for some peculiar aneurysms. Nonetheless, there is no documentation of aneurysm showing robust intracranial artifact on computed tomography or magnetic resonance imaging. CASE DESCRIPTION: Herein, we report a 45-year-old female with an IA showing a robust intracranial metal artifact. During surgery, the culprit lesion for the artifact was discovered to be hard plaque on the ventral part of the aneurysm. Craniotomy clipping and vessel reconstruction were successful, but minor vasospasm was observed postoperatively. Postoperative pathology and optical emission spectrometer analyses showed elevated iron and copper level in the plaque on the IA. After comparing with other aneurysm samples, we believe the overenriched local iron deposition contributed to the metal artifact on imaging. CONCLUSIONS: Taken together, accidental findings of intracranial metal artifacts on computed tomography and magnetic resonance imaging can be indicative to iron deposition on intracranial aneurysm. Neuroimaging using magnetic field should be performed with caution. Local accumulation of lysed products from erythrocyte might contribute to the occurrence of this enriched iron deposition, but further evidence regarding the pathogenesis of copper deposition should be provided. Surgically, measures should be taken to avoid perioperative complications like vasospasm and delayed cerebral ischemia. Future report of similar cases would be helpful in optimizing the treatment modality for the aneurysm with metallic plaque.

Long Noncoding RNA HULC Promoter Polymorphism rs1041279 Is Associated with an Increased Risk of Cervical Squamous Cell Carcinoma.

Hepatocellular carcinoma upregulated long noncoding RNA (HULC), identified as an oncogene in cervical cancer, is involved in not only the clinical stage, lymph node metastasis, and depth of cervical invasion but also outcome. In this study, we aimed to investigate the association between 3 polymorphisms (i.e., rs1041279, rs3005167, and rs7770772) in the promoter of HULC and the risk of cervical squamous cell carcinoma (CSCC). The polymorphisms were genotyped using the multiplex ligase detection reaction assay. The promoter activity was measured using the dual-luciferase reporter assay kit. The rs1041279 GG genotype and G allele revealed a significantly higher risk of CSCC compared with the rs1041279 CC genotype and C allele (GG vs. CC, adjusted OR = 1.79, 95% CI, 1.17-2.73, P = 0.007; G vs. C, adjusted OR = 1.36, 95% CI, 1.09-1.69, P = 0.006). Haplotype analysis revealed that the rs3005167C-rs7770772G-rs1041279C or rs3005167C-rs7770772G-rs1041279G haplotype had a significantly higher risk of CSCC compared to the rs3005167G-rs7770772G-rs1041279C haplotype (CGC vs. GGC, OR = 2.38, 95% CI, 1.53-3.75, P < 0.001; CGG vs. GGC, OR = 3.76, 95% CI, 2.12-6.68, P < 0.001). Dual-luciferase reporter assay showed that the rs1041279 G promoter resulted in higher transcriptional activity compared with the rs1041279 C (P < 0.01). Additionally, the rs1041279 GG genotype carriers had an increased level of HULC expression (P = 0.03). These findings suggest that the HULC rs1041279 may be a useful marker for the etiology of CSCC.

LINC00261 functions as a competing endogenous RNA to regulate BCL2L11 expression by sponging miR-132-3p in endometriosis.

Endometriosis is a benign disease but manifests with malignant features and limited treatment options. Women with endometriosis should not be ignored or patronized by the medical profession and society. In this regard, a major cultural change and searching for the optimum therapeutic regimen from multiple perspectives is needed in China even in the whole world. Long non-coding RNAs are crucial for various human diseases while its potential functions and mechanisms are largely unknown in endometriosis. LINC00261 was significantly downregulated in endometriosis tissues and our study indicated that it suppresses proliferation and invasion of endometriosis cells functionally in vitro. Insights of the mechanism of competitive endogenous RNAs were obtained from bioinformatic analysis, RIP, RNA pull-down and luciferase assays, which further confirmed that LINC00261 functions as a molecular sponge to regulate BCL2L11 expression by binding to miR-132-3p directly. These data defined LINC00261/miR-132-3p/BCL2L11 regulatory networks may be a novel therapeutic target for endometriosis.

Clinical efficacy of pelvic autologous tissue reconstruction in treating pelvic organ prolapse in 36 patients.

This study aims to search for a new, economic, convenient, and low recurrence rate operation for the surgical management of pelvic organ prolapse (POP). The clinical value of the operation for treating POP was determined through retrospective case series. The new operation was called, pelvic autologous tissue reconstruction.Women with symptomatic uterine prolapse, who required surgery, were recruited. A total of 97 women [stage III to IV, according to POP quantification (POP-Q) staging] were collected from January 2010 to December 2016. Among these women, 61 women underwent a traditional operation (TO, vaginal hysterectomy and vaginal anterior and posterior wall repair), while the remaining women underwent pelvic autologous tissue reconstruction.First, there was no statistically significant difference in intraoperative blood loss, indwelling urethral catheter time, in-hospital time, and the time of passage of gas through the anus between the pelvic autologous reconstruction (PAR) and TO groups (P > .05). The average operation time in the PAR group was significantly longer than that in the TO group (P < .05). Second, ultrasonic parameters before and after the operation between the 2 groups were compared. The postoperative rotation angle of the urethra (UR), posterior vesicourethral angle (PVA), and bladder neck descent (BND) significantly decreased in the PAR group (P < .05). There was no statistically significant difference in UR between before and 12 months after surgery in the TO group (P > .05). Furthermore, BND increased in the TO group at 12 months after the operation, compared with that at 3 months after the operation (P < .05). There was no significant difference in PVA and UR before the surgery and at 3 and 12 months after the surgery between the 2 groups (P > .05). In addition, BND was significantly smaller in the PAR group than in the TO group at 3 and 12 months after the surgery (P < .05). Third, there was no statistically significant difference in PFIQ-7 and PISG-12 in both groups after surgery.The stability of the pelvic floor structure was better in the PAR group than in the TO group. Furthermore, PAR is better for preventing the occurrence of pelvic floor prolapse and stress urinary incontinence after surgery.

Structure-based design, synthesis and in vitro antiproliferative effects studies of novel dual BRD4/HDAC inhibitors.

Histone acetylation marks play important roles in controlling gene expressions and are removed by histone deacetylases (HDACs). These marks are read by bromodomain and extra-terminal (BET) proteins, whose targeted inhibitors are under clinical investigation. BET and HDAC inhibitors have been demonstrated to be synergistically killing in Mycinduced murine lymphoma. Herein, we combine the inhibitory activities of BET and HDAC into one molecule through structure-based design method and evaluate its function. The majority of these synthesized compounds showed inhibitory activity against second bromdomains(BRD) of BRD4 and HDAC1. Among them, 16ae presented anti-proliferative effects against human acute myelogenous leukemia (AML) cell lines in vitro, and 16ae is confirmed to reduce the expression of Myc by Western blot analysis. Those results indicated that 16ae is a potent dual BRD4/HDAC inhibitor and deserves further investigation.