Comparison of Prone With Lithotomy Position in Removal of Posterior Myoma in Transvaginal Natural Orifice Endoscopic Surgery: A Prospective Cohort Study.

OBJECTIVE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is considered to have the advantages of completely scarless, less postoperative pain, earlier flatus, and faster postoperative recovery. However, posterior myoma are relatively difficult to operate through vNOTES in the conventional lithotomy position. Thus, we innovated the application of prone position in the removal of posterior myoma in vNOTES. The aim of this study is the comparison of myomectomy outcomes of patient for single posterior myoma in prone and lithotomy position. DESIGN: A single-center, prospective study. SETTING: A university teaching hospital. PATIENTS: A total of 81 patients with posterior myoma who underwent myomectomy in vNOTES from January 2021 to December 2022. INTERVENTIONS: The patients underwent myomectomy in vNOTES in prone or lithotomy position. MEASUREMENTS AND MAIN RESULTS: Among the patients who underwent vNOTES myomectomy, 29 (35.8%) were in the lithotomy position group, and 52 (64.2%) in the prone position group. Of note, 4 (4.9%) patients underwent a conversion to LESS during the operation-3 in the lithotomy and 1 in the prone position group. And a patient in the lithotomy position group underwent resurgery for hemostasis due to postoperative pelvic bleeding. Compared with the lithotomy position, prone position significantly shortens the operation time (12.3, 95% CI: 6.811, 17.761. p = .009) without increasing the complications and postoperative discomfort of patients. CONCLUSION: Compared to the lithotomy position, the prone position provides greater convenience for operation and exhibits a lower rate of surgical conversion during the removal of single posterior myomas via vNOTES. Further, for patients selecting vNOTES, surgeons need to conduct sufficient preoperative evaluation, timely hemostasis during surgery, and timely surgical conversion if necessary to ensure patient safety.

Prediction of anti-cancer drug synergy based on cross-matching network and cancer molecular subtypes.

At present, anti-cancer drug synergy therapy is one of the most important methods to overcome drug resistance and reduce drug toxicity in cancer treatment. High-throughput screening through deep learning can effectively improve the efficiency of discovering synergistic drugs. Nowadays, most of the existing deep learning algorithms for anti-cancer drug synergy prediction use deep neural networks and can only implicitly perform feature interaction. This study proposes a deep learning algorithm, named MolCross, which combines implicit feature interaction with explicit features to improve the accuracy of prediction of the anti-cancer drug synergy score. MolCross uses a deep autoencoder to extract features from high-dimensional input, uses the drug-specific subnetworks and cross-network to perform implicit feature interaction and explicit feature interaction respectively, and finally uses a synergy prediction network to combine the two feature interaction methods to obtain the final prediction results. We adopted a five-fold cross validation and compared MolCross with other four anti-cancer drug synergy prediction models. The results show that MolCross has better prediction performance than other models. MolCross also has good performance in terms of cross-cell line and cross-tissue type. Existing studies have demonstrated that cancer molecular subtypes have different sensitivities to targeted therapy. In this study, the features of cancer molecular subtype were introduced in the model using an embedding layer in MolCross to explore the effect of cancer molecular subtype on anti-cancer drug synergy. We also found that the cancer molecular subtype is one of the main factors affecting the synergy between drugs.

Loop-mediated isothermal amplification linked a nanoparticles-based biosensor for detecting Epstein-Barr virus.

Epstein-Barr virus (EBV) is a ubiquitous gamma herpesvirus that maintains a lifelong latent association with B lymphocytes. Here, a rapid and reliable diagnosis platform for detecting EBV infection, employing loop-mediated isothermal amplification (LAMP) combined with a gold nanoparticles-based lateral flow biosensors (AuNPs-LFB) (termed LAMP Amplification Mediated AuNPs-LFB Detection, LAMAD), was developed in the current study. A set of specific LAMP primers targeting the Epstein-Barr nuclear antigen (EBNA) leader protein (EBNA-LP) gene was designed and synthesized. Subsequently, these templates extracted from various pathogens and whole blood samples were used to optimize and evaluate the EBV-LAMAD assay. As a result, the limit of detection (LoD) of the EBV-LAMAD assay was 45 copies/reaction. The EBV-LAMAD assay can detect all representative EBV pathogens used in the study, and of note, no cross-reactions were observed with other non-EBV organisms. Moreover, the whole workflow of the EBV-LAMAD assay can be completed within 70 min, including rapid EBV template preparation, EBV-LAMP amplification, and AuNPs-LFB-mediated detection. Taken together, the EBV-LAMAD assay targeting the EBNA-LP gene is a rapid, simplified, sensitive, reliable, and easy-to-use detection protocol that can be used as a competitive potential diagnostic/screening tool for EBV infection in clinical settings, especially in basic laboratories in resource-limited regions. KEY POINTS: • A novel, simplified, and easy-to-use AuNPs-LFB biosensor was designed and prepared. • LAMP combined with an AuNPs-LFB targeting the novel EBNA-LP gene was established. • EBV-LAMAD is a rapid, sensitive, and reliable detection protocol for EBV infection.

The Nomogram Model and Factors for the Postoperative Mortality of Elderly Patients with Femoral Neck Fracture Undergoing Artificial Hip Arthroplasty: A Single-Institution 6-Year Experience.

OBJECTIVE: Artificial hip arthroplasty (AHA) is widely accepted in elderly patients with femoral neck fractures, but it is associated with high risk of death and various postoperative complications due to old age and accompanying chronic diseases. Therefore, this study aimed to explore the risk factors for death in elderly patients with femoral neck fractures after AHA and to establish a nomogram risk prediction model, which is expected to reveal high-risk patients and improve the postoperative quality of life and survival rate of patients. METHODS: Elderly patients who underwent AHA for femoral neck fractures in our hospital from September 2014 to May 2021were retrospectively analyzed. These patients were divided into a survival group and a death group according to their clinical outcomes. The following clinical data were recorded for the patients in the two groups: sex, age, underlying diseases, smoking and drinking history, preoperative nutritional risk score (NRS) and American Society of Anesthesiologists (ASA) score, as well as relevant indicators about the operation. These data were subject to univariate analysis and then logistic analysis to determine the risk factors of death. Subsequently, a nomogram risk prediction model was established and further validated with the receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test. Finally, the effects of predictive risk factors were analyzed using the Kaplan-Meier survival curve. RESULTS: Follow-up was completed by 260 patients, including 206 patients in the survival group and 54 patients in the death group; the overall death rate was 20.77%, and the follow-up time, age, postoperative 1, 3 and 5-year death rates were 3.47 ± 1.93 years, 75.32 ± 9.12 years, 5.77%, 12.51%, and 25.61%, respectively. The top three causes of death in 54 patients were respiratory disease, cerebrocardiovascular disease, and digestive disease, respectively. The logistic analysis indicated that elderly patients with femoral neck fractures, the risk factors for death after AHA were age ≥ 80 years, preoperative NRS ≥ 4, HB ≤ 90 g/L, CR ≥ 110 umol/L, and ASA score ≥ 3, as well as postoperative albumin ≤ 35 g/L, the nomogram was established, and then its predictive performance was successfully validated using the ROC curve (AUC = 0.814, 95% confidence interval = 0.749-0.879) and the Hosmer-Lemeshow test (p = 0.840). Furthermore, Kaplan-Meier survival curve analysis revealed that the abovementioned six indicators were correlated with the post-AHA survival time of elderly patients with femoral neck fractures (pLog Rank < 0.05). CONCLUSION: Old age, preoperatively high NRS and ASA score, anemia, poor renal function, and postoperative hypoproteinemia are the major risk factors for death in elderly patients with femoral neck fractures after AHA; they are also associated with postoperative survival. Early identification and effective interventions for optimization of modifiable risk factors are recommended to improve the postoperative quality of life and survival rates.

Inhibitory effects of Jasminum grandiflorum L. essential oil on lipopolysaccharide-induced microglia activation-integrated characteristic analysis of volatile compounds, network pharmacology, and BV-2 cell.

Neuroinflammation is considered to have a prominent role in the pathogenesis of Alzheimer's disease (AD). Microglia are the resident macrophages of the central nervous system, and modulating microglia activation is a promising strategy to prevent AD. Essential oil of Jasminum grandiflorum L. flowers is commonly used in folk medicine for the relief of mental pressure and disorders, and analyzing the volatile compound profiles and evaluating the inhibitory effects of J. grandiflorum L. essential oil (JGEO) on the excessive activation of microglia are valuable for its application. This study aims to explore the potential active compounds in JGEO for treating AD by inhibiting microglia activation-integrated network pharmacology, molecular docking, and the microglia model. A headspace solid-phase microextraction combined with the gas chromatography-mass spectrometry procedure was used to analyze the volatile characteristics of the compounds in J. grandiflorum L. flowers at 50°C, 70°C, 90°C, and 100°C for 50 min, respectively. A network pharmacological analysis and molecular docking were used to predict the key compounds, key targets, and binding energies based on the detected compounds in JGEO. In the lipopolysaccharide (LPS)-induced BV-2 cell model, the cells were treated with 100 ng/mL of LPS and JGEO at 7.5, 15.0, and 30 µg/mL, and then, the morphological changes, the production of nitric oxide (NO) and reactive oxygen species, and the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1 of BV-2 cells were analyzed. A total of 34 compounds with significantly different volatilities were identified. α-Hexylcinnamaldehyde, nerolidol, hexahydrofarnesyl acetone, dodecanal, and decanal were predicted as the top five key compounds, and SRC, EGFR, VEGFA, HSP90AA1, and ESR1 were the top five key targets. In addition, the binding energies between them were less than -3.9 kcal/mol. BV-2 cells were activated by LPS with morphological changes, and JGEO not only could clearly reverse the changes but also significantly inhibited the production of NO and reactive oxygen species and suppressed the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1. The findings indicate that JGEO could inhibit the overactivation of microglia characterized by decreasing the neuroinflammatory and oxidative stress responses through the multi-compound and multi-target action modes, which support the traditional use of JGEO in treating neuroinflammation-related disorders.

Guggulsterone Promotes Nasopharyngeal Carcinoma Cells Exosomal Circfip1L1 to Mediate miR-125a-5p/VEGFA Affecting Tumor Angiogenesis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism. METHODS: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 µmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs. RESULTS: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a- 5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis. CONCLUSIONS: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.

UV C Light from a Light-Emitting Diode at 275 Nanometers Shortens Wound Healing Time in Bacterium- and Fungus-Infected Skin in Mice.

Due to the changes in pathogenic species and the absence of research on topical skin antibiotics, the therapy of skin and soft tissue infections (SSTIs) is facing more and more severe challenges. It is particularly urgent to look for alternative therapies without induction of drug resistance. UV C (UVC) light within the range of 200 to 280 nm is one of the most common techniques used to kill and/or inactivate pathogenic microorganisms. However, the traditional most commonly used wavelength of 254 nm irradiated from a low-pressure mercury lamp is hazardous to human health, being both carcinogenic and damaging to eye tissues, which limits its applications in vivo. This research aimed to investigate the antimicrobial properties and influence of 275-nm UVC light from a light-emitting diode (UVC-LED light) on wound healing time. Five bacteria, three fungi, and scalded-mouse models combined with SSTIs were used to evaluate the antimicrobial effect in vitro and in vivo. 275-nm UVC-LED light inactivated both bacteria and fungi with a very short irradiation time in vitro and induced neither DNA damage nor epidermal lesions in the mice's skin. Furthermore, in mouse models of SSTIs induced by either methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans, the 275-nm UVC-LED light showed significant antimicrobial effects and shortened the wound healing time compared with that in the no-irradiation group. UVC-LED light at 275 nm has the potential to be a new form of physical therapy for SSTIs. IMPORTANCE As a common clinical problem, the therapy of SSTIs is facing growing challenges due to an increase in the number of drug-resistant bacteria and fungi. UV C (UVC) light sterilization has been widely used in all aspects of daily life, but there are very few reports about in vivo therapy using UVC light. It is well known that prolonged exposure to UVC light increases the possibility of skin cancer. In addition, it is also very harmful for eyes. UV irradiation with 254-nm UVC light can cause corneal damage, like thinning of the corneal epithelial layer, superficial punctate keratitis, corneal erosion, etc. In this study, we focused on looking for a more accessible light source and safer UVC wavelength, and 275-nm UVC LED light was chosen. We investigated its applicability for SSTIs therapy with relative skin safety and expected that it could be used as a new physical therapy method for SSTIs.

Transvaginal natural orifice endoscopic surgery for myomectomy: Can it be a conventional surgery?

Introduction: As a new minimally invasive surgery, transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has been proved to be suitable for the treatment of a variety of gynecological benign diseases. However, compared with other minimally invasive surgeries that have been widely used, such as conventional multiport laparoscopy and transumbilical laparoendoscopic single-site surgery (LESS), their advantages and disadvantages and how to choose are still unknown. The purpose of our study is to compare the advantages and disadvantages of the three minimally invasive surgeries in myomectomy and to provide theoretical basis for the wider development of vNOTES surgery. Material and methods: This retrospective study included 282 patients at our hospital who underwent laparoscopic myomectomy from May 2021 to March 2022. Based on the surgical approach, patients were classified into multiport, transumbilical LESS, and vNOTES groups. The patients' demographic characteristics and follow-up data were collected during the perioperative period and at 1 month postoperatively. Results: Among the three procedures, vNOTES had the shortest anal exhaust time but also the highest postoperative infection rate. Multiple linear regression analysis showed that the operative time increased by 3.5 min for each 1 cm increase in myoma, and intraoperative bleeding increased by approximately 12 ml. The average duration of single pores increased by 25 min compared to that of multiports, and the operative duration increased by 10.48 min for each degree of adhesion. Conclusions: For gynecologists who have mastered vNOTES, this procedure has the same efficacy and safety as the two existing minimally invasive surgeries in myomectomy, but it shows obvious advantages in postoperative recovery.

Whole-genome sequencing and comparative analysis of Helicobacter pylori GZ7 strain isolated from China.

Helicobacter pylori (H. pylori) is a Gram-negative pathogen as a carcinogen of the class Ι, with unique genetic diversity and wide geographic differences. The high incidence of gastric cancer in East Asia may be related to the bacterial genotype. It is of great significance that the genome of H. pylori in East Asia is widely collected. Therefore, we combined two sequencing technologies (PacBio and Illumina HiSeq 4000) and multiple databases to sequence and annotate the whole genome of H. pylori GZ7 isolated from a gastric cancer patient in Guizhou, China. Furthermore, this sequence was further compared with the genome sequence of 23 H. pylori strains isolated from different regions through collinearity comparison, specific gene analysis, phylogenetic tree construction, etc. The results showed that the genome of H. pylori GZ7 consists of 1,579,995 bp circle chromosomes with a GC content of 39.51%. This chromosome has 1,572 coding sequences, three antibiotic resistance genes, five prophages, and 198 virulence genes. The comparative genome analyses showed that H. pylori GZ7 has 53 specific genes compared to the other 23 strains. Most of these specific genes have not been annotated and characterized until now, whose research may provide insights into the biological activities of this strain. H. pylori GZ7 has the closest genetic relationship with H. pylori F30, and the farthest genetic relationship with H. pylori ELS37, which indicates that H. pylori genomes have geographical differences. This information may provide a molecular basis and guidance for constructing diagnostic methods for H. pylori and researching subsequent experiments.

Red Nucleus Interleukin-6 Evokes Tactile Allodynia in Male Rats Through Modulating Spinal Pro-inflammatory and Anti-inflammatory Cytokines.

Our previous studies have clarified that red nucleus (RN) interleukin (IL)-6 is involved in the maintenance of neuropathic pain and produces a facilitatory effect by activating JAK2/STAT3 and ERK pathways. In this study, we further explored the immune molecular mechanisms of rubral IL-6-mediated descending facilitation at the spinal cord level. IL-6-evoked tactile allodynia was established by injecting recombinant IL-6 into the unilateral RN of naive male rats. Following intrarubral administration of IL-6, obvious tactile allodynia was evoked in the contralateral hindpaw of rats. Meanwhile, the expressions of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 were elevated in the contralateral spinal dorsal horn (L4-L6), blocking spinal TNF-α, IL-1ß, or IL-6 with neutralizing antibodies relieved IL-6-evoked tactile allodynia. Conversely, the levels of anti-inflammatory cytokines transforming growth factor-ß (TGF-ß) and IL-10 were reduced in the contralateral spinal dorsal horn (L4-L6), an intrathecal supplement of exogenous TGF-ß, or IL-10 attenuated IL-6-evoked tactile allodynia. Further studies demonstrated that intrarubral pretreatment with JAK2/STAT3 inhibitor AG490 suppressed the elevations of spinal TNF-α, IL-1ß, and IL-6 and promoted the expressions of TGF-ß and IL-10 in IL-6-evoked tactile allodynia rats. However, intrarubral pretreatment with ERK inhibitor PD98059 only restrained the increase in spinal TNF-α and enhanced the expression of spinal IL-10. These findings imply that rubral IL-6 plays descending facilitation and produces algesic effect through upregulating the expressions of spinal pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 and downregulating the expressions of spinal anti-inflammatory cytokines TGF-ß and IL-10 by activating JAK2/STAT3 and/or ERK pathways, which provides potential therapeutic targets for the treatment of pathological pain.

Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis.

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58.

The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear. Our study used CRISPR/Cas 9 system to knockdown AUF1 in IHH4 and TPC1 cells. We noticed that the expression of TRIM58 and ZBTB2 were increased in the AUF1 knockdown IHH4 and TPC1 cells. When TRIM58 and ZBTB2 were inhibited by small hairpin RNAs (shRNAs) against TRIM58 (shTRIM58) and ZBTB2 (shZBTB2), respectively, the proliferation, migration, and invasion ability of the AUF1-knockdown IHH4 and TPC1 cells were increased. In addition, two ZBTB2 binding sites (-719~-709 and -677~-668) on TRIM58 promoter and two AUF1 binding sites (1250-1256 and 1258-1265) on ZBTB2 3'-UTR were identified. These results suggested that AUF1 affecting thyroid cancer cells via regulating the expression of ZBTB2 and TRIM58.

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3.

BACKGROUND: Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. METHODS: In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. RESULTS: IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. CONCLUSIONS: These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.

Benefits of Iron Chelators in the Treatment of Parkinson's Disease.

As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson's disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

TRIM29 inhibits miR-873-5P biogenesis via CYTOR to upregulate fibronectin 1 and promotes invasion of papillary thyroid cancer cells.

Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence, has a strong propensity for neck lymph node metastasis. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Tripartite motif protein 29 (TRIM29) is dysregulated in various cancer and functions as oncogene or tumor suppressor in discrete cancers. In this study, we found that both TRIM29 and fibronectin 1 (FN1) were upregulated with positive correlation in PTC tissues. Neither overexpression nor downregulation of TRIM29 altered the proliferation of PTC cells significantly. Overexpression of TRIM29 significantly promotes, while knockdown of TRIM29 significantly decreases migration and invasion by regulating FN1 expression in PTC cells. In terms of mechanism, we found that TRIM29 altered the stability of FN1 mRNA via regulation of miR-873-5p expression. The current study also demonstrated that long non-coding RNA (LncRNA) CYTOR suppressed maturation of miR-873-5p via interaction with premiR-873, and TRIM29 decreased miR-873-5p via upregulation of CYTOR. This study suggests that involvement of TRIM29 in migration and invasion in PTC cells may reveal potential metastatic mechanism of PTC and represent a novel therapeutic target and strategy.

Red nucleus IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1ß through the JAK2/STAT3 and ERK signaling pathways.

We previously reported that interleukin (IL)-6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal-regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor-α (TNF-α) and IL-1ß in RN IL-6-mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL-6 three weeks after SNI, increased protein levels of both TNF-α and IL-1ß were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF-α and IL-1ß were closely correlative with IL-6 and suppressed by intrarubral injection of a neutralizing antibody against IL-6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up-regulations of local TNF-α and IL-1ß. Further experiments indicated that intrarubral injection of exogenous IL-6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF-α and IL-1ß. Pretreatment with AG490 could block IL-6-induced tactile hypersensitivity and suppress the up-regulations of both TNF-α and IL-1ß. However, injection of PD98059 in advance only inhibited the upregulation of IL-1ß, but not TNF-α. These findings indicate that RN IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1ß. IL-6 induces the expression of TNF-α through the JAK2/STAT3 pathway, and the production of IL-1ß through the JAK2/STAT3 and ERK pathways.

The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans.

The extensive and repetitive use of antifungal drugs has led to the development of drug-resistant Candida albicans. Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach to combat drug-resistant microbes. This study evaluated the photodynamic effects mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, on azole-sensitive and azole-resistant C. albicans in vitro. AE exhibited no significant dark toxicity, but in the presence of light, effectively inactivated C. albicans cells in a concentration-dependent manner. The uptake of AE by fungal cells was investigated by confocal laser scanning microscopy (CLSM), and the results showed that AE possessed stronger ability to enter into C. albicans cells following light irradiation. Transmission electron microscopy analysis suggested that AE-mediated aPDT could induce damage to the cell wall, cytoplasm, and nucleus. Damage to the surface of C. albicans was observed by scanning electron microscopy. These results suggest that AE is a potential PS for use in aPDT of drug-resistant C. albicans strains, and AE-mediated aPDT shows promise as an antifungal treatment.

Hypocrellin B-Mediated Photodynamic Inactivation of Gram-Positive Antibiotic-Resistant Bacteria: An In Vitro Study.

Background: The search for alternative therapeutics against antibiotic-resistant bacteria is highly desirable. A promising approach is photodynamic antimicrobial chemotherapy. Objective: This work evaluated the photodynamic inactivation (PDI) efficacy of hypocrellin B (HB) on Gram-positive antibiotic-resistant bacteria. Methods: PDI efficacy of HB on Gram-positive standard and antibiotic-resistant Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumonia and Gram-negative Escherichia coli and Klebsiella pneumoniae was assessed. HB photoactivity on biofilms formed by the Gram-positive bacteria and its cytotoxicity on mammalian CT26 cells were also investigated. Results: HB showed no obvious dark toxicity, but provided concentration-dependent inactivation of bacteria and mammalian cells. After irradiation with 72 J/cm2 light, 100 µM of HB achieved about 7 log10 reductions in bacterial survival of Gram-positive strains, but yielded only 2 log10 reductions in bacterial survival of Gram-negative strains. Gram-positive bacteria were as susceptible to PDI in biofilms as in planktonic suspensions, but the efficacy was attenuated. Conclusions: The results suggested that HB could serve as a potential antibacterial photosensitizer against Gram-positive antibiotic-resistant bacteria.

High-sensitivity determination of cadmium and lead in rice using laser-induced breakdown spectroscopy.

Stability and sensitivity of toxic elements determination is still unsatisfactory in agricultural product using laser-induced breakdown spectroscopy (LIBS). A simple and low cost sample pretreatment method named solid-liquid-solid transformation method was proposed in this work. The target analytes of cadmium (Cd) and lead (Pb) from rice samples were prepared through ultrasound assisted extraction in hydrochloric acid solution. The solution was dropped on the glass slide after centrifuging process and was further dried on a heater. Finally, the glass slide contained the analytes was carried out for LIBS determination. Compare with conventional pellet method, the spectral intensity of Cd and Pb element were enhanced significantly using LIBS. The limits of detection were 2.8 and 43.7 µg/kg, respectively. The limits of quantification were 9.3 and 145.7 µg/kg, respectively. The results demonstrated that LIBS coupled with ultrasound assisted extraction should be a promising tool to detect toxic elements in rice.

Determination of antimony in soil using laser-induced breakdown spectroscopy assisted with laser-induced fluorescence.

Antimony (Sb) in soil is attracting attention in the research community due to its potential toxicity and carcinogenicity. Traditional methods of detecting Sb lack the ability of rapid and nondigestion analysis, which hinders their development and application. Moreover, it is still a challenge for laser-induced breakdown spectroscopy (LIBS) to detect Sb in soil due to the weak intensities and intense interference of spectral lines. Here, LIBS, assisted with laser-induced fluorescence (LIBS-LIF), was used to selectively enhance the Sb's characteristic spectral lines under optimal parameters. The quantitative analysis performance was notably improved with a determination coefficient (R2) of 0.991, the limit of detection of 0.221 µg/g, and root mean square error of cross validation of 3.592 µg/g. These results demonstrate that LIBS-LIF has the potential to realize the rapid and accurate analysis of Sb in soil.