Effects of exercise therapy on disability, mobility, and quality of life in the elderly with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. METHODS: We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. RESULTS: Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = - 1.75, 95% CI - 2.59, - 0.92, p < 0.05), Oswestry disability index (ODI) (WMD = - 9.42, 95% CI - 15.04, - 3.79, p < 0,005), short-form 36-item health survey physical composite summary (SF-36PCS) (WMD = 7.07, 95% CI 1.01, 13.14, p < 0.05), short-form 36-item health survey mental composite summary (SF-36MCS) (WMD = 7.88, 95% CI 0.09, 15.67, p < 0.05), and timed up and go test (TUG) (WMD = - 0.92, 95% CI - 2.22, 0.38, p < 0.005). CONCLUSION: Exercise therapy effectively improved VAS, ODI, and SF-36 indexes in the elderly. Based on the subgroup, when designing the exercise therapy regimen, aerobics, strength, and mind-body exercise (≥ 12 weeks, ≥ 3 times/week, ≥ 60 min) should be considered carefully, to ensure the safety and effectiveness for the rehabilitation of CLBP patients. More high-quality trials are needed in future to confirm the effect of exercise on SF-36 and TUG indexes.

Effects of Different Exercise Modes on Gait Performance of Parkinson's Disease Patients: A Systematic Review and Network Meta-Analysis.

Gait disturbances are among the main symptoms of Parkinson's disease (PD) and can increase fall risk. In this study we aimed to systematically evaluate the effects of different exercise modes on gait indexes of PD patients. We conducted a review and network meta-analysis of randomized controlled trials in studies listed in Web of Science, MEDLINE, EMBASE, PsycINFO, Cochrane Library, ClinicalTrailS.gov, and China National Knowledge Infrastructure databases from their inception to October 23, 2021. Eligible studies were randomized controlled trials investigating the effect of exercise on gait index by using the Timed Up and Go test, (TUG), stride length, stride cadence, or 6 Minutes Walking Test (6MWT). We used Review Manager 5.3 to evaluate the quality of the included literature, and we used Stata 15.1 and R-Studio for the network meta-analysis. We assessed the relative ranking of therapies by the surface under the cumulative ranking possibilities. In 159 studies, there were 24 exercise interventions. Compared with the control group, 13 exercises showed significant improvements on the TUG; six exercises were significantly better for improving stride length; only one exercise was better for improving stride cadence; and four exercises were better for improving the 6MWT. The surface under the cumulative ranking curves suggested that Pilates, body weight support treadmill training, resistance training, and a multidisciplinary exercise program were preferable for gains on TUG, stride length, stride cadence, and 6MWT. This meta-analytic review found that exercise therapies bring obvious benefits to gait indexes of patients with PD, and the efficacy of exercise therapies varied with different types of exercise and outcome indexes.

Effects of aquatic exercises on physical fitness and quality of life in postmenopausal women: an updated systematic review and meta-analysis.

Objective: In the present systematic review and meta-analysis, we aimed to evaluate and update the effects of aquatic exercise on physical fitness and quality of life (QoL) in postmenopausal women. Methods: The databases Cochrane Library, PubMed, Web of Science, and MEDLINE were searched for randomized controlled trials (RCTs) on the topic from inception to July 2022. The GetData software was used to extract data from the published images. RevMan5.4 software was used for statistical analysis. Data are expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). I2 index was employed for heterogeneity. Egger's test was used to assess publication bias. We evaluated the methodological quality of included studies using the Physiotherapy Evidence Database scale. Results: We included 594 participants in 16 RCTs (19 comparison groups). The results indicated that aquatic exercise can significantly improve lower limb strength (LLS), upper limb strength (ULS), agility, flexibility, and overall QoL. No significant effects were found on aerobic capacity. Subgroup-analysis results indicated that aquatic exercise only significantly improved LLS, ULS, agility, and flexibility in postmenopausal women < 65 years of age. However, aquatic exercise improves the overall QoL both in postmenopausal women < 65 years and ≥ 65 years. Aquatic resistance exercise significantly improves LLS, ULS, agility and flexibility. In addition, aquatic aerobic exercise can effectively increase LLS, and combined aquatic aerobic and resistance exercise can enhance the overall QoL. Conclusions: Aquatic exercise can effectively improve physical fitness and overall QoL in postmenopausal women, but has limited effects on aerobic capacity; thus, it is highly recommended in postmenopausal women.

Comparing the effects of different exercises on blood pressure and arterial stiffness in postmenopausal women: A systematic review and meta-analysis.

The present study aimed to compare the efficacy of different exercises on systolic blood pressure (SBP), diastolic blood pressure (DBP), and aortic pulse wave velocity (PWV) in postmenopausal women. We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, Web of Science, PubMed, and Cochrane library databases, up to July 2022. The randomized controlled trials (RCTs) were selected following the inclusion criteria. We assessed study quality with the PEDro scale. The Stata software was used for statistical analysis. Twenty-three papers (26 RCTs) and 729 participants were included. Meta-analysis demonstrated that exercise decreased SBP (WMD = -6.74 mmHg, 95%CI: -9.08, -4.41, p = 0.000), DBP (WMD = -4.13 mmHg, 95%CI: -5.78, -2.48, p = 0.000) and aortic PWV (WMD = -0.79 m/s, 95%CI: -1.02, -0.56, p = 0.000). Aerobic exercise can significantly decrease SBP (WMD = -7.97 mmHg, 95%CI: -12.99, -2.60, p = 0.003) and DBP (WMD = -5.97 mmHg, 95%CI: -8.55, -3.39, p = 0.000). Resistance exercise can significantly decrease SBP (WMD = -5.62 mmHg, 95%CI: -9.00, -2.23, p = 0.001), DBP (WMD = -1.87 mmHg, 95%CI: -2.75, -0.99, p = 0.000) and aortic PWV (WMD = -0.67 m/s，95%CI: -0.98, -0.36, p = 0.000). Combined aerobic and resistance exercise can significantly decrease SBP (WMD = -5.42 mmHg, 95%CI: -10.17, -0.68, p = 0.025). The efficacy of mind-body exercise (Tai Chi/Yoga) on SBP, DBP, and aortic PWV were not obvious (p > 0.05). Exercise significantly improved SBP, DBP, and aortic PWV in postmenopausal women. Aerobic exercise decreased SBP and DBP. Resistance exercise decreased SBP, DBP, and aortic PWV. Additionally, further research is required to confirm the efficacy of mind-body exercise (Tai Chi/Yoga) on blood pressure and arterial stiffness.

[Application of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis].

PURPOSE: To explore the value of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis. METHODS: A total of 120 patients with localized periodontitis who underwent dental implantation in the Department of Stomatological, Shanghai Pudong New Area People's Hospital from August 2021 to September 2022 were selected. According to the way of postoperative infection prevention, the patients were divided into control group and experimental group, with 60 patients in each group. The control group was orally given roxithromycin capsules, and the experimental group was locally coated with minocycline hydrochloride ointment and metronidazole gel. The incidence of postoperative infection and complications was compared between the two groups. The modified gingival creval bleeding index (mSBI), periodontal probing depth (PD) and modified plaque index (mPLI) of the patients were examined by periodontal probe. Serum C-reactive protein (CRP) level was determined by immunoturbidimetry and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) level was determined by ELISA. SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: Good healing rate of the experimental group was 91.67% higher than that of the control group 73.33%, postoperative infection rate was 8.33% and complication rate was 6.67% in the experimental group, significantly lower than that of the control group (26.67% and 20.00%), respectively (P＜0.05). After treatment, the level of CRP, TNF-α and IL-6 in the experimental group were significantly lower than those in the control group (P＜0.05). At 3 and 6 months after treatment, mSBI, mPLI and PD in the experimental group were significantly lower than those in the control group(P＜0.05). CONCLUSIONS: The administration of minocycline hydrochloride and metronidazole in patients with localized periodontitis undergoing implantation can reduce oral inflammatory response, reduce postoperative infection and other complications, and improve periodontal health.

Effects of Low Back Pain Exercises on Pain Symptoms and Activities of Daily Living: A Systematic Review and Meta-Analysis.

Our objective in this paper was to systematically review evaluations of the effects of exercises on pain symptoms and activities of daily living (ADL) in middle-aged and elderly patients with low back pain (LBP). We searched Web of Science, PubMed, EBSCO, and China National Knowledge Internet (CNKI) databases for randomized controlled trials (RCTs) on this topic. We evaluated the methodological quality of included articles using the Physiotherapy Evidence Database (PEDro) scale, and we statistically analyzed these studies using RevMan software. We reviewed 18 RCTs (23 comparison groups) with a total of 910 participants, and our meta-analysis confirmed that exercises significantly improved both pain and ADLs measured on visual analog scales (VAS) (SMD = -0.91, 95% CI: [-1.3, -0.52], p < 0.00001) and on the Oswestry Disability Index (ODI) (SMD = -2.07, 95% CI: [-3.19, -0.96], p < 0.00001). We conclude that exercises can reduce pain severity and improve ADL capacity in middle-aged and elderly persons with LBP, confirming that exercise can serve as a medical intervention for these indivdiuals. However, given the high heterogeneity of responses among individual participants, there remains a need for further study.

Antimicrobial peptide AR-23 derivatives with high endosomal disrupting ability enhance poly(l-lysine)-mediated gene transfer.

BACKGROUND: pH-sensitive peptides are a relatively new strategy for conquering the poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improves its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection. METHODS: In the present study, we investigated the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 with respect to enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in the AR-23 sequence with Glu one-by-one. RESULTS: The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking, the transfection efficiency and the cytotoxicity of the polyplexes were determined. Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in the AR-23 sequence greatly improved poly(l-lysine)-mediated gene transfection efficiency at the same time as maintaining low cytotoxicity. CONCLUSIONS: The results indicate that replacement of positively-charged residues with sufficient Glu residues may be considered as a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

Heparanase Facilitates PMA-Induced Megakaryocytic Differentiation in K562 Cells via Interleukin 6/STAT3 Pathway.

Heparanase (HPSE) is an endo-ß-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.

Heparanase Promotes Tumor Growth and Liver Metastasis of Colorectal Cancer Cells by Activating the p38/MMP1 Axis.

Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. In this study, we examined the expression of HPSE in different colorectal cancer (CRC) cell lines. Gene manipulation was applied to reveal the effect of HPSE on proliferation, invasion, and metastasis of CRC. Knockdown of HPSE resulted in decreased cell proliferation in vitro, whereas overexpression of HPSE resulted in the opposite phenomenon. Consistently, in vivo data showed that knockdown of HPSE suppressed tumor growth of CRC. Furthermore, knockdown of HPSE inhibited invasion and liver metastasis in vitro and in vivo. RNA-sequencing analysis was performed upon knockdown of HPSE, and several pathways were identified that are closely associated with invasion and metastasis. In addition, HPSE is positively correlated with MMP1 expression in CRC, and HPSE regulates MMP1 expression via p38 MAPK signaling pathway. In conclusion, our data demonstrate that HPSE knockdown attenuated tumor growth and liver metastasis in CRC, implying that HPSE might serve as a potential therapeutic target in the treatment of CRC.

Papillary cystadenoma of the parotid gland: A case report.

BACKGROUND: Papillary cystadenoma is a rare benign epithelial tumor of the salivary gland, which is characterized by papillary structures and oncocytic cells with rich eosinophilic cytoplasm. We found only one case of papillary cystadenoma in nearly 700 cases of salivary gland tumors. Our case was initially mistaken for a tumor of the right temporomandibular joint (TMJ) capsule rather than of parotid gland origin. Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) should be carefully studied, which allows for appropriate preoperative counseling and operative planning. CASE SUMMARY: Here, we report an unusual case of a 54-year-old woman with a parotid gland papillary cystadenoma (PGPC) that was misdiagnosed as a tumor of the right TMJ capsule. She was initially admitted to our hospital due to a mass anterior to her right ear inadvertently found 5 d ago. Preoperative CT and MRI revealed a well circumscribed tumor that was attached to the right TMJ capsule. The patient underwent a resection through an incision for TMJ, but evaluation of an intraoperative frozen section revealed a benign tumor of the parotid gland. Then we removed part of the parotid gland above the temporal facial trunk. The facial nerve was preserved. Postoperative histopathological findings revealed that the tumor was PGPC. No additional treatment was performed. There was no recurrence during a 20-mo follow-up period. CONCLUSION: The integrity of the interstitial space around the condyle in MRI or CT should be carefully evaluated for parotid gland or TMJ tumors.

[Effects of Dnmt1 and Dnmt3b in mucoepidermoid carcinoma of salivary glands].

PURPOSE: To investigate the effects of DNA methyltransferase in mucoepidermoid carcinoma of human salivary glands tissues. METHODS: Forty-three samples from mucoepidermoid carcinoma of salivary glands and 17 normal salivary gland tissues were collected from January 2010 to September 2013. Immunohistochemistry and Western blot were used to detect the expression of Dnmt1 and Dnmt3b in normal tissues and specimen of mucoepidermoid carcinoma of salivary glands. The data were analysed with SPSS 22.0 software package. RESULTS: The positive expression rate of Dnmt1 in mucoepidermoid carcinoma tissue was 37.21%, and that in normal salivary gland tissues was 17.65%, there was no significant difference between them; the positive expression rate of Dnmt3b in mucoepidermoid carcinoma tissue was 83.72%, which was significantly higher than that in normal salivary gland tissue (11.76%, P<0.01). However, there was no significant correlation between high expression of Dnmt1 and Dnmt3b and clinicopathological parameters. CONCLUSIONS: Dnmt3b may play a role in the tumorigenesis of mucoepidermoid carcinoma in salivary glands.

Both maternal and paternal risk factors for term singleton low birthweight infants in rural Chinese population: a population-based, retrospective cohort study.

No large population-based study has focused on both maternal paternal risk factors for low birthweight (LBW) in China. We aimed to identify parental risk factors associated with LBW.A population-based, retrospective cohort study was conducted on 202,725 singleton infants at 37-42 weeks. These term singleton newborns were classified as LBW with birthweight ≤2500 g(TLBW) and normal birthweight between 50th to 97th percentile (TNBW 50th-97th) according to Chinese singleton norms. Multiple logistic regression analyses were used to find those parental risk factors of LBW by comparing two groups. TLBW and TNBW(50th-97th) occupied 4.8% and 70.8% of the study population, respectively. Logistic regression showed a significant association with positive maternal hepatitis B surface antigen (RR = 1.979, P = 0.047), irregular folic acid intake (RR = 1.152, P = 0.003), paternal history of varicocele (RR = 2.404, P = 0.003) and female babies (RR = 1.072, P = 0.046). Maternal smoking, hypertension and history of stillbirth were found related to LBW but no statistically significant. Positive maternal hepatitis B surface antigen, irregular folic acid intake, paternal history of varicocele had a negative effect on birth weight. Measures are necessarily taken to avoid them to improve pregnancy outcomes. Further studies should be done to investigate each detailed risk factors on LBW.

CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of patients.

OBJECTIVE: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma. PATIENTS AND METHODS: We determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation. RESULTS: In our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls. CONCLUSION: Our study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma.

Seroepidemiology of Syphilis Infection among 2 Million Reproductive-age Women in Rural China: A Population-based, Cross-sectional Study.

BACKGROUND:: Quantifying syphilis prevalence is important for planning interventions and advocating for resources on syphilis. However, data on large sample studies regarding the prevalence of syphilis among reproductive-age women in rural China were not available for analysis. The aim of the study was to determine the prevalence, epidemiological characteristics, and related factors of syphilis infection among reproductive-age women in rural China. METHODS:: Data were obtained from a nationwide, population-based, cross-sectional study under the National Free Preconception Health Examination Project which covered all the 31 provinces in Mainland China. Women intending to get pregnant within the next 6 months were enrolled between January 1, 2010, and December 31, 2012. Sociodemographic, gynecological and obstetric characteristics, and other relevant information were obtained through face-to-face interviews. Treponema pallidum particle agglutination assay test was used to detect positive samples of syphilis. Univariate and multivariate logistic regressions were performed to assess the associations between syphilis seropositivity and related factors. RESULTS:: The overall seroprevalence of syphilis (SPS) among the 2,044,126 women who received syphilis screening test during 2010-2012 was 0.37% (95% confidence interval [CI]: 0.36-0.37%). The SPS appeared 0.24% (95% CI: 0.23-0.26%) and 0.66% (95% CI: 0.59-0.72%) in women at 21-24 and 40-44 years of age, respectively, showing an increase of SPS, parallel with age, and the difference was significant. SPS was significantly higher in ethnic minorities than that in Han nationality (0.58% vs. 0.35%, respectively, odds ratio [OR] = 1.41, 95% CI: 1.30-1.53) and higher in workers than that in farmers (0.45% vs. 0.36%, respectively, OR = 1.27, 95% CI: 1.14-1.41). Women with primary school or below level had a higher SPS as compared to those with college or above educational level (0.61% vs. 0.32%, respectively, OR = 2.49, 95% CI: 2.14-2.89), and the increase reversely correlated with the levels of education. Women whose spouses were syphilis seropositive had significant greater risk (OR = 48.26, 95% CI: 44.38-52.48) as compared those whose spouses were seronegative. Women who reported having had a history of sexually transmitted infections were more likely to be tested positive for serological syphilis (OR = 27.17, 95% CI: 20.44-36.11) as compared to those without. CONCLUSIONS:: High SPS is seen among reproductive-age women in rural China that calls for targeted interventions on syphilis prevention and control in this target population, with emphasis on those who are 35 years of age and above, less educated, being minor ethnicity, workers, and living in the western regions of China.

Gemcitabine-induced heparanase promotes aggressiveness of pancreatic cancer cells via activating EGFR signaling.

Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR. In addition, we showed that the NF-κB pathway mediated the gemcitabine-induced HPA1 expression. Importantly, we found that an HPA1 inhibitor attenuated gemcitabine-induced invasion of PC cells. Finally, we showed that HPA1 was of negative prognostic value for PC patients. Taken together, our results demonstrated that gemcitabine-induced HPA1 promotes proliferation and invasion of PC cells through activating EGFR, implying that HPA1 may serve as promising therapeutic target in the treatment of PC.

The prevalence and risk factors of preterm small-for-gestational-age infants: a population-based retrospective cohort study in rural Chinese population.

BACKGROUND: Preterm birth and small for gestational age (SGA) are strong indicators of neonatal adverse outcomes. With the growing importance of preterm SGA infants, we aim to evaluate the prevalence and risk factors for preterm SGA in China. METHOD: We analyzed the data of parents and infants from a population-based cohort research of the free National Pre-pregnancy Checkups Project (NPCP) in rural China. Only singleton live births that occurred between 24 weeks +0 days and 36 weeks +6 days of pregnancy were included in this study. SGA was defined as birth weight less than the 10th percentile of the reference birth-weight-for-gestational-age population. A multiple logistic regression model was built using the statistically significant variables from the 371 variables in the questionnaire. RESULTS: A total of 11,474 singleton, preterm, live-birth infants were included. Of the total infants, 317 (2.77%) were preterm SGA infants. A higher risk of preterm SGA infants was observed among mothers who were on oral contraceptives (OR: 8.162, 95% CI: 1.622-41.072), mothers who had syphilis (OR: 12.800, 95% CI: 1.250-131.041), and mothers with a high eosinophil percentage (OR: 13.292, 95% CI: 1.282-135.796). Maternal intake of folic acid at least 3 months before pregnancy (OR: 0.284, 95% CI:0.124-0.654) and paternal intake of egg and meat (OR: 0.097,95% CI:0.030-0.315) were protective factors. Compared with North China, the incidence of preterm SGA infants was higher in South China. CONCLUSION: Preterm SGA infants were associated with both maternal and paternal factors.

Design of pH-sensitive peptides from natural antimicrobial peptides for enhancing polyethylenimine-mediated gene transfection.

BACKGROUND: Poor endosomal release is a major barrier of polyplex-mediated gene transfection. Antimicrobial peptides (AMPs) are commonly used to improve polyethylenimine (PEI)-mediated gene transfection by increasing endosomal release. In the present study, we designed novel pH-sensitive peptides that highly enhance transfection efficiency compared to their parent peptides. METHODS: Two analogues of melittin (Mel) and RV-23 (RV) were synthesized by replacing the positively-charged residues in their sequences with glutamic acid residues. The pH-sensitive lysis ability of the peptides, the effect of the peptides on physicochemical characteristics, the intracellular trafficking, the transfection efficiency, and the cytotoxicity of the polyplexes were determined. RESULTS: The acidic peptides showed pH-sensitive lytic activity. The hemolytic activity of acidic peptides at pH 5.0 was higher than that at pH 7.4. The incorporation of acidic peptides did not affect the DNA binding ability of PEI but affected the physicochemical characteristics of the PEI/DNA polyplexes, which may be beneficial for endosomal release and gene transfection. The incorporation of acidic peptides into PEI/DNA polyplexes enhanced the PEI-mediated transfection efficiency corresponding to up to 42-fold higher luciferase activity compared to that of PEI alone. CONCLUSIONS: The results of the present study indicate that replacement of positively-charged residues with glutamic acid residues in the AMP sequence yields pH-sensitive peptides, which enhance the transfection efficiency of PEI/DNA polyplexes in various cell lines.

Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.

AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents.

RV-23, a Melittin-Related Peptide with Cell-Selective Antibacterial Activity and High Hemocompatibility.

RV-23 is a melittin-related antibacterial peptide (MRP) with lower cytotoxicity than either melittin or AR-23, another MRP. The aim of this study was to explore the mechanism of RV- 23's antibacterial selectivity and its hemocompatibility. The results showed that all the peptides exhibited lytic activity against Staphylococcus aureus and Escherichia coli, with RV-23 showing the highest potency. Moreover, RV-23 had lower cytotoxicity than melittin or AR-23 at their minimal inhibitory concentration. In addition, CD experiments showed that melittin, RV-23, and AR-23 all had a typical α-helical structure, and RV-23 had the lowest α-helix content. The structural information showed that RV-23 has the lowest hydrophobicity and highest hydrophobic moment. Because hydrophobicity and α-helix content are believed to correlate with hemolysis, the results indicate that the selective lytic activity against bacteria of RV-23 may be due to its low hydrophobicity and α-helicity, which lead to low cytotoxicity without affecting antibacterial activity. Furthermore, RV-23 did not affect the structure and function of blood components such as red blood cells, platelets, albumin, and the blood coagulation system. In conclusion, RV-23 is a cell-selective antibacterial peptide with high hemocompatibility due to its unique structure.

Quantification of α-Gal Antigen Removal in the Porcine Dermal Tissue by α-Galactosidase.

The α-Gal (Galα1,3-Galß1-4GlcNAc-R) epitope, the major xenoantigen, is the first barrier in a porcine-to-man tissue and organ xenotransplantation. The elimination or reduction of the α-Gal epitopes is therefore an important step for a successful xenotransplantation. The present study is to evaluate the α-Gal elimination in the porcine skin with α-galactosidase treatment, and to assess two methods (immunohistochemistry and inhibition ELISA) that may be used in quality control for quantifying the extent of the α-Gal elimination. Enzymatic cleavage in a single-step process is extremely efficient and affordable at eliminating the α-Gal epitope even in a tissue as dense as the porcine dermis. The cost of enzymatic cleavage is found to be less than US$7 for a 10 × 10 cm piece of porcine skin (0.5 mm thick) or about US$140 for 100 g of 3-dimensional soft tissues. After enzymatic cleavage, the α-Gal-positive immunostaining was essentially undetectable in enzyme-treated porcine skin. The inhibition rate constant of the monoclonal anti-Gal antibody M86 binding to α-Gal-bovine serum albumin in ELISA was reduced from 15.0 ± 4.3 (n = 10) to 6.1 ± 2.6 (n = 7) after enzyme treatment, in comparison to 4.4 ± 1.8 (n = 9) background inhibition of decellularized human skin (the ultimate negative control), which demonstrates ∼ 84% elimination of α-Gal epitopes in treated porcine skin. To examine the suitability of two detection methods for the routine quality control application, comparative studies were made with control and enzyme-treated porcine skin, porcine skin from the α-Gal knockout animal, as well as decellularized human skin. The data show that the traditional immunohistochemistry and, to a less extent, the inhibition ELISA with further modifications can be used as quality control tools in the production and selection of biocompatible bioprosthetic devices. The biological evaluation of enzyme-treated porcine skin is ongoing with a small animal model and a nonhuman primate model.