Copper exposure induces trophoblast cell cuproptosis by up-regulating lnc-HZ11.

Copper pollution has attracted global environmental concern. Widespread Cu pollution results in excessive Cu accumulation in human. Epidemiological studies and animal experiments revealed that Cu exposure might have reproductive toxicity. Cuproptosis is a recently reported Cu-dependent and programmed cell death pattern. However, the mechanism by which copper exposure might cause cell cuproptosis is largely unknown. We chose trophoblast cells as cell model and found that copper exposure causes trophoblast cell cuproptosis. In mechanism, copper exposure up-regulates lnc-HZ11 expression levels, which increases intracellular Cu2+ levels and causes trophoblast cell cuproptosis. Knockdown of lnc-HZ11 efficiently reduces intracellular Cu2+ levels and alleviate trophoblast cell cuproptosis, which could be further alleviated by co-treatment with DC or TEPA. These results discover novel toxicological effects of copper exposure and also provide potential target for protection trophoblast cells from cuproptosis in the presence of excessive copper exposure.

Colorectal Cancer Stem Cells and Targeted Agents.

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.

Case Report: A novel de novo variant of COL1A1 in fetal genetic osteogenesis imperfecta.

Objective: Osteogenesis imperfecta (OI) is a rare genetic disorder. Clinical severity is heterogeneous. The purpose of this study was to investigate the genetic characteristics of a fetus with OI by whole exome sequencing (WES) and identify the cause of the disease. Methods: In this study, a fetus with osteogenic dysplasia was referred to our hospital. DNA was extracted from the aborted fetal tissue and peripheral blood of the parents. To identify the pathogenic genes, we conducted the trio-WES using DNA. A de novo variant in the COL1A1 gene is suspected to be the cause of the OI phenotype. We used Sanger sequencing for validation and various bioinformatics methods (such as SIFT, PolyPhen2, Mutation Taster, conservative analysis, SWISS Model, glycosylation site prediction, and I-Mutant 2.0) for analysis. Results: Both WES and Sanger sequencing identified a novel de novo variant of COL1A1 (c. 1309G>A, p. Gly437Ser) in a fetus with OI. Bioinformatic analysis showed that the affected residue, p. Gly437, was highly conserved in multiple species and predicted that the variant was deleterious and may have an impact on protein function. This variant is present in highly conserved glycine residues of Gly-X-Y sequence repeats of the triple helical region of the collagen type I α chain, which may be the cause of OI. Conclusion: This study revealed that the c.1309G>A (p. Gly437Ser) variant in the COL1A1 gene may be the genetic cause of fetal OI in this case. The discovery of this variant enriched the variation spectrum of OI. WES improves the accurate diagnosis of fetal OI, and doctors can provide patients with appropriate genetic counseling.

A New Antirotation Strategy of K-Wire Tension Band Therapy for Patellar Fracture.

Background: Patellar fracture is a common phenomenon observed in orthopedic clinics. Many methods have been shown to be effective in the fixation of patellar fracture. However, there are few studies on the antirotation effect of these methods. The purpose of this study is to present a new strategy of K-wire tension band therapy for patellar fracture and explore the antirotation effect of the modified tension band method on patellar fracture. Methods: A retrospective clinical observation study was conducted on 75 patients with patellar fracture. Totally, 46 patients were enrolled to the traditional group, who received the traditional K-wire tension band therapy. The modified group included 29 patients on whom our new strategy was implemented. The operation time, intraoperative blood loss, and fracture healing time were collected to compare the two operations and the knee society score (KSS) scores after the operations, and complications were recorded and retrieved to indicate the effectiveness of the two treatments. Results: The preoperative baseline data (gender, age, fracture types) of the two groups showed no significant statistical difference. Similarly, there was no significant difference in the operation time, intraoperative blood loss, and fracture healing time between the two groups. The KSS clinical scores 1 year after operation was 90 (84, 95) for the traditional group as compared with 99 (97, 100) for the modified group (p < 0.05). The KSS functional scores 1 year after operation in the two groups were 90 (65, 90) and 100 (90, 100) (p < 0.05). The incidences of complications due to the rotation of K-wires in the traditional group and the modified group were 76.1% (35 of 46) and 6.9% (2 of 29) with a significant statistical difference (p < 0.05). Conclusion: This study shows that our modified tension band therapy is an effective strategy for antirotation in the treatment of patellar fracture and proves that it can achieve better clinical outcomes than the traditional K-wire tension band method. This new strategy may be a safe and effective clinical technique for the treatment of patellar fracture. However, more prospective randomized controlled trials with larger sample sizes are still needed to further prove its efficacy.

Release of inhalable particles and viable microbes to the air during packaging peeling: Emission profiles and mechanisms.

Packaging is necessary for preserving and delivering products and has significant impacts on human health and the environment. Particle matter (PM) may be released from packages and transferred to the air during a typical peeling process, but little is known about this package-to-air migration route of particles. Here, we investigated the emission profiles of total and biological particles, and the horizontal and vertical dispersion abilities and community structure of viable microbes released from packaging to the air by peeling. The results revealed that a lot of inhalable particles and viable microbes were released from package to the air in different migration directions, and this migration can be regulated by several factors including package material, effective peeling area, peeling speed and angles, as well as the characteristics of the migrant itself. Dispersal of package-borne viable microbes provides direct evidence that viable microbes, including pathogens, can survive the aerosolization caused by peeling and be transferred to air over different distances while remaining alive. Based on the experimental data and visual proof in movies, we speculate that nonbiological particles are package fibers fractured and released to air by the external peeling force exerted on the package and that microbe dispersal is attributed to surface-borne microbe suspension by vibration caused by the peeling force. This investigation provides new information that aerosolized particles can deliver package-borne substances and viable microbes from packaging to the ambient environment, motivating further studies to characterize the health effects of such aerosolized particles and the geographic migration of microbes via packaging.

IL-25-induced activation of nasal fibroblast and its association with the remodeling of chronic rhinosinusitis with nasal polyposis.

BACKGROUND AND OBJECTIVE: Interleukin (IL)-25 has been shown to play an important role in the pathogenesis of chronic rhinosinusitis with nasal polyps. Nasal polyps are associated with chronic inflammation of the mucous membranes in the paranasal sinuses and are involved in extracellular matrix (ECM) accumulation. The aim of this study is to evaluate the effects of IL-25 on myofibroblast differentiation, ECM production and the expression of matrix metalloproteinases in nasal polyp derived fibroblasts (NPDFs) and to determine the molecular mechanism underlying these processes. MATERIALS AND METHODS: A total of 40 patients were enrolled in this study for Immunofluorescence studies. Expression of IL17 receptor B was evaluated by real time reverse transcription polymerase chain reaction (PCR) in NPDFs. NPDFs were stimulated with IL-25 for 48 h in the presence or absence of mitogen-activated protein kinase (MAPK) and NF-κB inhibitors or small interfering RNAs (siRNA). The protein levels of fibrosis active mediators were examined using western blotting. Fibroblast migration was evaluated with a scratch assay. The total collagen amount was analyzed with the Sircol collagen assay. RESULTS: IL-25 induced α-SMA, fibronectin, and MMP-1 and -13, which were dependent on IL-17RB. IL-25 also induced activation of NF-κB and mitogen-activated protein kinase (MAPKs). By using the specific inhibitor of ERK, p38, JNK and NF-κB (U, SB, SP and Bay), we found that IL-25-induced expressions of α-SMA, fibronectin, and MMPs was regulated by the signaling pathways of MAPKs and NF-κB. IL-25 also induces α-SMA, fibronectin, and MMPs expression through IL-17RB-dependent pathways in NPDFs. The increased migration ability induced by IL-25 was suppressed by the specific inhibitors of MAPKs and NF-κB. CONCLUSION: Our data indicate that IL-25 induced myofibroblast differentiation, fibronectin production, and MMP-1 and -13 expressions through the signaling pathways of MAPKs and NF-κB. in NPDFs and increased expression of IL-25 were also involved in the pathogenesis of nasal polyposis by affecting nasal fibroblasts in chronic rhinosinusitis with nasal polyps.

Role of Interleukin-10 on Nasal Polypogenesis in Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND AND OBJECTIVES: Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP. MATERIALS AND METHODS: Thirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinated tissues (UT) were collected for analysis. Dispersed NP cells (DNPCs) were cultured in the presence or absence of IL-25 and IL-10, and a flow cytometric assay was performed to identify the constitutive cell populations of the DNPCs. Murine NP (n = 18) models were used for the in vivo experiments. Real-time PCR, immunohistochemistry, western blotting analysis and ELISA were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules. RESULTS: The mRNA expression levels of IL-10, IL-5, IL-17A, IL-25 and interferon gamma (IFN-γ) were significantly higher in the NP tissues than in the UT tissues. Strong positive correlations were observed between IL-10 and a variety of inflammatory cytokines (IL-5, IL-17A, IL-25, IFN-γ) and inflammation-associated molecules (B-cell activating factor; BAFF, CD19). Other than the IL-25 to IL-10 ratio, the expression ratios of the other measured inflammatory cytokines to IL-10 were significantly lower in the CRSwNP group than in the CRSsNP or control groups. Administrating IL-25 into the cultured DNPCs significantly increased the production of IL-10, but administrating IL-10 had no effect on the production of IL-25. CONCLUSION: Increased expression of IL-10, IL-10 related inflammatory cytokine, and IL-10 related B cell activation indicated that IL-10, a potent anti-inflammatory cytokine, has a pivotal role in the pathogenesis of CRSwNPs.

Effects of triamcinolone-impregnated nasal dressing on subjective and objective outcomes following endoscopic sinus surgery.

The aim of this study was to compare the effects of triamcinolone (TA)- and saline-soaked biodegradable nasal dressing on subjective symptoms, wound healing and improvement of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after undergoing endoscopic sinus surgery (ESS). The study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 80 patients undergoing bilateral ESS for CRSwNP were enrolled and randomly assigned to two groups. Nasal dressing was impregnated with normal saline in the control group, while patients received triamcinolone-impregnated dressing in the TA group. Sino-Nasal Outcome Test 20 (SNOT-20) and Korean Version of the Sniffin' Stick (KVSS) II test were used to assess the patients' condition preoperatively and at postoperative 1 and 3 months. Lund-Kennedy (L-K) and perioperative sinus endoscopy (POSE) scores were assessed on postoperative months 1, 2, and 3. There were significant differences between the control group and the TA group in terms of postoperative L-K scores and POSE scores at 1 and 2 months. The postoperative endoscopic scores were significantly decreased in the TA group compared to the control at 1 month. Olfactory functions were significantly improved at postoperative 3 months (p = 0.0099) compared to the preoperative score in the TA group. Significant improvement in the olfactory functions among anosmic and hyposmic patients at postoperative 1 month (p = 0.0475) and 3 months (p = 0.0019) compared to their preoperative olfactory function score was observed only in the TA group. TA-impregnated dressing had a significant advantage over saline-soaked dressing with regard to postoperative wound healing and improvement of olfactory function.