The application of indocyanine green in guiding prostate cancer treatment.

Objective: Indocyanine green (ICG) with near-infrared fluorescence absorption is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment. It has strong optical absorption in the near-infrared region, where light can penetrate deepest into biological tissue. We sought to review its value in guiding prostate cancer treatment. Methods: All related literature at PubMed from January 2000 to December 2020 were reviewed. Results: Multiple preclinical studies have demonstrated the usefulness of ICG in identifying prostate cancer by using different engineering techniques. Clinical studies have demonstrated the usefulness of ICG in guiding sentinel node dissection during radical prostatectomy, and possible better preservation of neurovascular bundle by identifying landmark prostatic arteries. New techniques such as adding fluorescein in additional to ICG were tested in a limited number of patients with encouraging result. In addition, the use of the ICG was shown to be safe. Even though there are encouraging results, it does not carry sufficient sensitivity and specificity in replacing extended pelvic lymph node dissection during radical prostatectomy. Conclusion: Multiple preclinical and clinical studies have shown the usefulness of ICG in identifying and guiding treatment for prostate cancer. Larger randomized prospective studies are warranted to further test its usefulness and find new modified approaches.

Experiences in managing different consequences of forgotten ureteral stents.

Purpose: We reported the different consequences of forgotten stents and share our managing experiences. Patients and Methods: From July 2011 to August 2019, eight patients (five men and three women) with forgotten encrusted ureteral stents were treated by different endoscopic procedures in our center. Plain-film radiography (kidney, ureter, and bladder [KUB]) and computed tomography were used to evaluate the position of stents, the site of encrustation, and the stone burden. Various sole or combined endoscopic techniques including percutaneous nephrolithotomy, retrograde ureteroscopic lithotripsy, and cystolitholapaxy were used to achieve stent removal. Results: The average age of the patients was 50.9 years (range: 25-72 years). The mean indwelling time of the stents was 32.9 months (range: 12-83 months). Mean stent stone burden was 15 mm × 10 mm. Three patients had stent stone burden larger than 20 mm. Three patients had a preoperative positive urine culture before treatment. The stent was fragmented in two patients. The ureteral stents and related stones were successfully removed without any complications by a sole or combined endoscopic techniques with stone-free status achieved in all patients. There is no complications occurred. Conclusion: Forgotten stents can lead to complicated urinary tract calculi, stent encrustation, urinary tract infection, vesicoureteric reflux, and even ureteral polyps. Various sole or combined endourological techniques can be used to manage the forgotten encrusted ureteral stents.

New method of internal fixation in laparoscopic Tenckhoff catheter placement.

BACKGROUND: Despite obvious advantages of peritoneal dialysis (PD), mechanical complications are responsible for the failure of PD at early stage. Suture fixation in laparoscopic PD catheter method could reduce mechanical complications. In our study, a simple method to fix PD catheter was developed. METHODS: Tenckhoff catheter placement was performed in 49 consecutive patients. In the technique, only two trocars were used. With the help of syringe needle and forceps, a loop of silk was prepared at the abdominal wall. The PD catheter was thread through the loop. The silk ligature was tied subcutaneously keeping the catheter suspended from the abdominal wall. Primary outcomes were catheter-related complications. Secondary outcomes were 6-month catheter survival rates and death within 30 days. Data were analyzed retrospectively. RESULTS: The average operation time was 49.7 ± 15.8 min. Minimum follow-up time was 6 months. No catheter displacement or hernia was detected. One patient had omental wrapping after silk suture rupture, 2 patients had outflow obstruction, and 3 patients had leakage. No one died within 30 days postoperatively. Catheter survival was 95.8% at 6 months. CONCLUSIONS: The method we described greatly reduced the risk of catheter displacement and omental wrap. Also, the required instrument and laparoscopic skill were simple.

Genome-wide CRISPR-Cas9 screening identifies the CYTH2 host gene as a potential therapeutic target of influenza viral infection.

Host genes critical for viral infection are effective antiviral drug targets with tremendous potential due to their universal characteristics against different subtypes of viruses and minimization of drug resistance. Accordingly, we execute a genome-wide CRISPR-Cas9 screen with multiple rounds of survival selection. Enriched in this screen are several genes critical for host sialic acid biosynthesis and transportation, including the cytohesin 2 (CYTH2), tetratricopeptide repeat protein 24 (TTC24), and N-acetylneuraminate synthase (NANS), which we confirm are responsible for efficient influenza viral infection. Moreover, we reveal that CYTH2 is required for the early stage of influenza virus infection by mediating endosomal trafficking. Furthermore, CYTH2 antagonist SecinH3 blunts influenza virus infection in vivo. In summary, these data suggest that CYTH2 is an attractive target for developing host-directed antiviral drugs and therapeutics against influenza virus infection.

Starchy vegetable intake in the first trimester is associated with a higher risk of gestational diabetes mellitus: a prospective population-based study.

OBJECTIVE: The purpose of this study was to evaluate the association between starchy vegetable consumption and subgroup consumption in the first trimester and the risk of gestational diabetes mellitus (GDM). METHODS: A prospective study (n = 1444) was conducted in China. Dietary information was assessed by 24-hour dietary recalls for three days and then we calculated the consumption of total starchy vegetable and its subgroups, including (1) potato and (2) other starchy vegetable (pumpkin, lotus root, yam, taro, water chestnut, pea, and cowpea). GDM was diagnosed according to the results of 75-g two-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. A modified log-binomial regression was used to estimate RRs and 95% CIs of GDM risk. RESULTS: Among the 1444 participants in our study, 520 were diagnosed with GDM. The adjusted RRs (95% CIs) for GDM from the lowest to the highest quartiles of total starchy vegetable consumption were 1.00 (reference), 1.29 (1.06, 1.57), 1.13 (0.93, 1.40), and 1.26 (1.02, 1.56), respectively; p for trend = .032. For potato, the RR of GDM risk was 1.32 for the highest potato intake quartile compared with the lowest quartile (95% CI 1.07-1.64, p for trend = .003). In addition, we did not observe an association between other starchy vegetable intakes and GDM risk. CONCLUSIONS: A higher consumption of total starchy vegetables and potatoes in the first trimester is associated with a greater risk of GDM.

Measurement of Tremor on Arteriovenous Fistulas with a Flexible Capacitive Sensor.

Arteriovenous fistula (AVF) is a widely used vascular access for hemodialysis in clinical. It is a great challenge to monitoring the status of AVF in daily life due to acute AVF stenosis may occur on unnoticeable occasions, such as sleeping. Inspiring tremor is almost always accompanied by a healthy AVF, which can be adopted as an essential physiological sign for AVF monitoring. Hence, a fistula tremor measurement system based on a flexible capacitive pressure sensor is designed in this study. The sensor consists of polydimethylsiloxane(PDMS) dielectric layers, electrode layers, ground layers, and shielding layers. The PDMS layers are fabricated as cross superposition transverse microstructure film to enhance dielectric constant and sensitivity of the sensor. The isolation shielding layers and ground layers guarantee the sensing chain is noise-free. A microcontroller embedded AD7746 measurement circuit is designed for signal acquisition. We test our prototype on the wrists of healthy volunteers and AVF on dialysis patients separately. The pulse signals and AVF tremor signals are clear and distinguishable. The sensor and measurement system have excellent potential in wearable AVF monitoring.

Circular RNA circZNF652 is overexpressed in osteoarthritis and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN.

Circular RNA circZNF652 promotes LPS-induced inflammation, contributing to the development of osteoarthritis (OA), indicating the potential involvement of circZNF652 in OA. This study was carried to explore the involvement of circZNF652 in OA. RT-qPCR was performed to analyse the expression of circZNF652 and PTEN mRNA in synovial fluid samples from 60 OA patients and 60 healthy controls. Correlations between circZNF652 and PTEN mRNA were analysed by Pearson's correlation coefficient. Overexpression and siRNA silencing of circZNF652 were achieved in chondrocytes, followed by performing RT-qPCR and Western blot to analyse the expression of PTEN. The role of circZNF652 and PTEN in regulating the apoptosis of chondrocytes induced by LPS was analysed by cell apoptosis assay. We found that circZNF652 was overexpressed in OA and positively correlated with PTEN, MMP13, and NF-KB mRNA. In chondrocytes, circZNF652 overexpression increased the expression of PTEN, MMP13, and NF-KB; circZNF652 siRNA silencing decreased the expression of PTEN, MMP13, and NF-KB. Moreover, circZNF652 and PTEN positively regulated the apoptosis of chondrocytes induced by LPS. PTEN overexpression reversed the inhibitory effects of circZNF652 siRNA silencing on cell apoptosis. Therefore, circZNF652 is overexpressed in OA and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN.

The relationship between ApoE gene polymorphism and the efficacy of statins controlling hyperlipidemia.

OBJECTIVE: To explore the relationship between ApoE gene polymorphism and clinical efficacy of statins on lipidemia. METHODS: Peripheral venous blood was obtained from 220 patients with hyperlipidemia who were admitted to the outpatient department of our hospital. The potential relationship between ApoE gene polymorphism and clinical effect of statins was analyzed. RESULTS: In the three isomers (E2, E3, E4) of ApoE, expression level of ApoE protein in ApoE4 gene carriers was significantly different from that in E2 or E3 gene carriers (both P<0.05). At the same time, both the decrease rate of total cholesterol (TC) in blood lipid and low density lipoprotein cholesterol (LDL-C) and the rise rate of high density lipoprotein cholesterol (HDL-C) in ApoE4 carriers after taking statins were much lower than those in non-ApoE4 patients (P<0.05). CONCLUSION: ApoE gene polymorphism is associated with hyperlipidemia and has certain influence on the clinical efficacy of statins in treatment of hyperlipidemia.

[A Prospective Study of the Relationship Between Dietary Patterns during the Second Trimester of Pregnancy and Gestational Weight Gain].

OBJECTIVE: To study dietary patterns during the second trimester of pregnancy and to investigate the relationship between dietary patterns and gestational weight gain (GWG). METHODS: A prospective cohort study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and child health care institution in Chengdu city. Food items and quantities were collected at 8-14, 24-28, 32-36 weeks of gestation by using the 3-day 24-hour dietary recall and energy intakes were calculated. Dietary patterns during the second trimester were established by factor analysis and factor scores were calculated. The weight of pregnant women was measured at 8-14, 24-28 weeks of gestation and 1 week before delivery, and the total GWG and the GWG rates in the second and third trimesters were calculated. Multiple linear regression analyses were used to analyze the association between dietary patterns and GWG. RESULTS: A total of 1 004 samples were included. Three dietary patterns were identified: Milk-egg-whole grain pattern, Beverage-dessert pattern and Traditional pattern. The average total GWG was (13.2±4.5) kg. The average weight gain rate was (0.4±0.2) kg/week in the second trimester. The average weight gain rate was (0.5±0.3) kg/week in the third trimester. After adjusting for confounding factors including maternal age, body mass index before pregnancy, dietary energy intake, physical activity, multiple linear regression analysis showed that the factor score of Beverage-dessert pattern was positively associated with the total GWG and the weight gain rate in the third trimester ( ß=0.370, 95% confidence interval ( CI): (0.103, 0.636), P=0.007; ß=0.014, 95% CI: (0.000, 0.027), P=0.049, respectively), and the factor score of Traditional pattern was negatively associated with the total GWG ( ß=-0.285, 95% CI: (-0.555, -0.015), P=0.039). There was no association between the Milk-egg-whole grain pattern and GWG. CONCLUSION: Dietary patterns during the second trimester of pregnancy are associated with GWG. The Beverage-dessert pattern may increase the total GWG and weight gain rate in the third trimester. The traditional pattern may help control the total GWG.

[Associations of Dairy Consumption during Pregnancy and Neonatal Birth Body Mass: a Prospective Study].

OBJECTIVE: To investigate the dairy product intake during pregnancy in Southwest China and to explore its relationship with neonatal birth body mass. METHODS: A prospective study was conducted to select healthy singleton pregnant women at 8-14 weeks of gestation in a maternal and fetal health care institution in Chengdu City. Dairy product consumption during the first, second, third trimester of pregnancy were collected by 24-hour dietary recalls at 8-14 weeks, 24-28 weeks and 32-36 weeks of pregnancy, respectively, and the total milk intake and milk consumption rate were calculated. According to the dietary guidelines for Chinese pregnant women (2016), the recommended amount of milk (300 g/d) was used as the standard to calculate the compliance rate. The respondents were divided into three groups: no dairy consumption group, insufficient dairy consumption group and suitable dairy consumption group. The gestational age at delivery and neonatal birth body mass were collected by the hospital information system. Logistic regression model was used to analyze the association between milk intake during pregnancy and neonatal birth body mass. RESULTS: A total of 962 pregnant women were included. The average milk intake in the first, second and third trimester of pregnancy were 125.0 (0, 236.1) g/d, 208.3 (0, 284.7) g/d and 250.0 (150.0, 416.7) g/d, respectively, with the compliance rates of 12.6%, 33.2% and 48.4%, respectively. The average neonatal birth body mass was (3 225.0±399.8) g. The incidence of small for gestational age (SGA) and large for gestational age (LGA) was 8.3% and 3.9%, respectively. Compared with no dairy consumption group in the second trimester of pregnancy, the risk of SGA was lower in suitable dairy consumption group (odds ratio (OR)=0.786, 95% confidence interval (CI): 0.385-0.976). Compared with no dairy consumption group in the third trimester of pregnancy, the risk of SGA was lower in insufficient dairy consumption group and suitable dairy consumption group (OR=0.672, 95%CI: 0.477-0.821 and OR=0.497, 95%CI: 0.116-0.807, respectively). No association was observed between milk intake in the first trimester and neonatal birth body mass, and milk intake in the second and third trimester of pregnancy was not associated with the risk of LGA. CONCLUSION: Insufficient milk intake of pregnant women is a significant problem in southwest China and needs to be improved. Milk intake during pregnancy is associated with neonatal birth body mass, and increased milk intake in the second and third trimester of pregnancy may reduce the risk of SGA.

The effect of an intensive patients' education program on anxiety, depression and patient global assessment in diabetic foot ulcer patients with Wagner grade 1/2: A randomized, controlled study.

This study aimed to synthetically evaluate the impact of intensive patients' education program (IEP) on anxiety, depression and patient global assessment (PGA) in diabetic foot ulcer (DFU) patients.One hundred eighty DFU patients with Wagner grade 1 and Wagner grade 2 were consecutively recruited in this randomized, controlled study and randomly assigned to IEP group (N = 90) or control group (N = 90) as 1:1 ratio. In the IEP group, patients received the IEP and usual care, and patients in the control group received usual care only. IEP included educating patients and their family members, supervising patients' harmful habits and diets, psychological care for the patients and establishing a patient-physician-nurse WeChat group. Hospital Anxiety and Depression Scale-anxiety/depression (HADS-A/D) and Zung Self-Rating Anxiety/depression Scale (SAS/SDS) were applied to assess anxiety/depression at M0-M3. PGA score was also assessed at M0-M3.For anxiety assessment, IEP group presented decreased HADS-A/SAS scores at M2/M3 and increased HADS-A/SAS score changes (M3-M0) compared to control group. For depression assessment, IEP group displayed reduced HADS-D/SDS scores at M2/M3 and raised SDS score change (M3-M0) compared to control group. Moreover, IEP group exhibited reduced PGA score at M1/M2/M3 and elevated PGA score change (M3-M0) compared to control group. Further subgroup analyses disclosed that IEP reduced HADS-A/SAS/HADS-D/PGA scores at M3 and elevated these score changes (M3-M0) in patients with Wagener grade 2 but not Wagener grade 1.IEP ameliorates anxiety, depression and PGA in DFU patients with Wagner grade 2 but not Wagner grade 1.

Solution NMR structure of CGL2373, a polyketide cyclase-like protein from Corynebacterium glutamicum.

Protein CGL2373 from Corynebacterium glutamicum was previously proposed to be a member of the polyketide_cyc2 family, based on amino-acid sequence and secondary structure features derived from NMR chemical shift assignments. We report here the solution NMR structure of CGL2373, which contains three α-helices and one antiparallel ß-sheet and adopts a helix-grip fold. This structure shows moderate similarities to the representative polyketide cyclases, TcmN, WhiE, and ZhuI. Nevertheless, unlike the structures of these homologs, CGL2373 structure looks like a half-open shell with a much larger pocket, and key residues in the representative polyketide cyclases for binding substrate and catalyzing aromatic ring formation are replaced with different residues in CGL2373. Also, the gene cluster where the CGL2373-encoding gene is located in C. glutamicum contains additional genes encoding nucleoside diphosphate kinase, folylpolyglutamate synthase, and valine-tRNA ligase, different from the typical gene cluster encoding polyketide cyclase in Streptomyces. Thus, although CGL2373 is structurally a polyketide cyclase-like protein, the function of CGL2373 may differ from the known polyketide cyclases and needs to be further investigated. The solution structure of CGL2373 lays a foundation for in silico ligand screening and binding site identifying in future functional study.

Excessive gestational weight gain in the first trimester is associated with risk of gestational diabetes mellitus: a prospective study from Southwest China.

OBJECTIVE: To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women. DESIGN: A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range. SETTING: Southwest China. PARTICIPANTS: Pregnant women (n 1910) in 2017. RESULTS: After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8-1·2, 0·8-1·2 and 0·35-0·70 kg for underweight, normal-weight and overweight/obese women, respectively. CONCLUSIONS: Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.

Backbone and side chain resonance assignments of the C-terminal domain of human TGIF1.

TGIF1 is an essential regulator of cell differentiation in various biological processes, and is associated with holoprosencephaly and many cancers. The C-terminal domain of TGIF1 that was originally defined as repressive domain 2 can interact with a variety of proteins, such as transcription factor Smad2 and co-repressor Sin3A, to mediate the regulative roles of TGIF1 in diverse cell signaling pathways. However, the recognition mechanism of TGIF1 C-terminal domain for different interacting proteins remains unknown. Here, we report the nearly complete 1H, 13C, and 15N backbone and side chain resonance assignments of TGIF1 C-terminal domain (residues 256-375), laying a foundation for further research on the structure-function relationship of TGIF1.

Construction of a mavs-inactivated MDCK cell line for facilitating the propagation of canine distemper virus (CDV).

Canine distemper is a highly contagious disease of wild and domestic carnivores. Obtaining of a suitable cell line for canine distemper virus (CDV) propagation is very important for field CDV isolation and vaccine antigen preparation. However, the cell line currently developed cell lines for CDV propagation are a marmoset lymphoid cell line (B95a), which could cause the virus to potentially infect human cells, and canine SLAM-expressing Vero cells, which may cause the virus to lose virulence. Therefore, a canine cell line constructed for efficient CDV propagation would be attractive. In the present study, a Madin-Darby Canine Kidney Epithelial (MDCK) cell line with mavs (mitochondrial antiviral signaling) inactivation was constructed by CRISPR/Cas9 technology. The interferon-I response induced by poly(I:C), an analogue of viral RNA, was significantly blocked in the constructed cell line, designated MDCK-KOmavs. Moreover, the propagation of a filed CDV strain was approximately 100 times higher in MDCK-KOmavs cells than in wild-type MDCK cells. Therefore, in the present study, a canine cell line facilitating CDV propagation was successfully constructed, and the results suggested that the constructed canine cell line was more efficient than the wild-type cell line for the isolation of field CDVs. In addition, the rapid propagation of CDVs to high titers in the constructed MDCK-KOmavs cell line indicated that this cell line could also be an alternative cell line for the preparation of vaccine antigens.

Tantalum nanoparticles reinforced polyetheretherketone shows enhanced bone formation.

Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the properties of PEEK. By adding nanoparticles, fibers, etc., elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1 wt% to 9 wt%). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vitro and in vivo, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants.

Telerehabilitation in the Treatment of Frozen Shoulder: A Case Report.

Background and objectives: Frozen shoulder is a common musculoskeletal condition. Telerehabilitation has seen emerging use in a variety of conditions. This case report aims to investigate the feasibility of adopting telerehabilitation in treating frozen shoulder. Case presentation: A 43-year old female presented with frozen shoulder of insidious onset. She underwent four sessions of physiotherapy. Sessions two and three were telerehabilitation sessions; the initial and final sessions were conducted in-person. Results: The subject was compliant with all exercises prescribed during her rehabilitation and achieved all rehabilitation goals in four sessions. She was then discharged from physiotherapy. Conclusion: Telerehabilitation is feasible in treating frozen shoulder. One barrier to implementation of telerehabilitation includes the lack of technical skills and knowledge despite the high prevalence of technology in today's society. Telerehabilitation increases accessibility and ease of rehabilitation. Telerehabilitation can be considered for segments of the population that are most inclined to use technology.

Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss.

Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways are triggered by receptor activator of NF-κB ligand (RANKL), inflammatory factors, and oxidative stress. Previous studies have indicated that the common flavanone glycoside compound hesperetin exhibits anti-inflammatory and antioxidant activity by inhibition of NF-κB and MAPK signaling pathways. However, the direct relationship between hesperetin and osteolysis remain unclear. In the present study, we investigated the effects of hesperetin on lipopolysaccharide (LPS)-induced osteoporosis and elucidated the related mechanisms. Hesperetin effectively suppressed RANKL-induced osteoclastogenesis, osteoclastic bone resorption, and F-actin ring formation in a dose-dependent manner. It also significantly suppressed the expression of osteoclast-specific markers including tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1. Furthermore, it inhibited osteoclastogenesis by inhibiting activation of NF-κB and MAPK signaling, scavenging reactive oxygen species, and activating the nuclear factor E2 p45-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway. Consistent with in vitro results, hesperetin effectively ameliorated LPS-induced bone loss, reduced osteoclast numbers, and decreased the RANKL/OPG ratio in vivo. As such, our results suggest that hesperetin may be a great candidate for developing a novel drug for destructive bone diseases such as periodontal disease, tumor bone metastasis, rheumatoid arthritis, and osteoporosis.

A Label-Free Quantitative Proteomic Analysis of Mouse Neutrophil Extracellular Trap Formation Induced by Streptococcus suis or Phorbol Myristate Acetate (PMA).

Streptococcus suis (S. suis) ranks among the five most important porcine pathogens worldwide and occasionally threatens human health, particularly in people who come into close contact with pigs or pork products. An S. suis infection induces the formation of neutrophil extracellular traps (NETs) in vitro and in vivo, and the NET structure plays an essential role in S. suis clearance. However, the signaling pathway by which S. suis induces NET formation remains to be elucidated. In the present study, we used a label-free quantitative proteomic analysis of mouse NET formation induced by S. suis or phorbol myristate acetate (PMA), a robust NET inducer. Greater than 50% of the differentially expressed proteins in neutrophils infected by S. suis showed similar changes as observed following PMA stimulation, and PKC, NADPH oxidase, and MPO were required for NET formation induced by both stimuli. Because PMA induced robust NET formation while S. suis (MOI = 2) induced only weak NET formation, the association between the inducer and NET formation was worth considering. Interestingly, proteins involved in peptidase activity showed significant differential changes in response to each inducer. Of these peptidases, MMP-8 expression was obviously decreased in response to PMA, but it was not significantly changed in response to S. suis. A subsequent study further confirmed that MMP-8 activity was inversely correlated with NET formation induced by both stimuli. Therefore, the present study provides potentially important information about the manner by which neutrophils responded to the inducers to form NETs.