Therapeutic potential of ginseng leaf extract in inhibiting mast cell-mediated allergic inflammation and atopic dermatitis-like skin inflammation in DNCB-treated mice

Ginseng leaves are known to contain high concentrations of bioactive compounds, such as ginsenosides, and have potential as a treatment for various conditions, including fungal infections, cancer, obesity, oxidative stress, and age-related diseases. This study assessed the impact of ginseng leaf extract (GLE) on mast cell-mediated allergic inflammation and atopic dermatitis (AD) in DNCB-treated mice. GLE reduced skin thickness and lymph node nodules and suppressed the expression and secretion of histamine and pro-inflammatory cytokines. It also significantly lowered the production of inflammatory response mediators including ROS, leukotriene C4 (LTC4), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). GLE inhibited the phosphorylation of MAPKs (ERK, P38, JNK) and the activation of NF-κB, which are both linked to inflammatory cytokine expression. We demonstrated that GLE’s inhibitory effect on mast cell-mediated allergic inflammation is due to the blockade of the NF-κB and inflammasome pathways. Our findings suggest that GLE can be an effective therapeutic agent for mast-cell mediated and allergic inflammatory conditions

Investigation of the dorsolateral branch of the posterior intercostal artery for use as the pedicle of a free flap: A cadaveric study and case series

Background The dorsolateral branch of the posterior intercostal artery (DLBPI) can be easily found while harvesting a latissimus dorsi (LD) musculocutaneous flap for breast reconstruction. However, it remains unknown whether this branch can be used for a free flap and whether this branch alone can provide perfusion to the skin. We examined whether the DLBPI could be reliably found and whether it could provide sufficient perfusion. Methods We dissected 10 fresh cadavers and counted DLBPIs with a diameter larger than 2 mm. For each DLBPI, the following parameters were measured: distance from the lateral margin of the LD muscle, level of the intercostal space, distance from the spinal process, and distance from the inferior angle of the scapula. Results The DLBPI was easily found in all cadavers and was reliably located in the specified area. The average number of DLBPIs was 1.65. They were located between the seventh and eleventh intercostal spaces. The average length of the DLBPI between the intercostal space and the LD muscle was 4.82 cm. To assess the perfusion of the DLBPIs, a lead oxide mixture was injected through the branch and observed using X-rays, and it showed good perfusion. Conclusions The DLBPI can be used as a pedicle in free flaps for small defects. DLBPI flaps have some limitations, such as a short pedicle. However, an advantage of this branch is that it can be reliably located through simple dissection. For women, it has the advantage of concealing the donor scar underneath the bra band

House of Commons Library: Briefing paper: Number 07147, 13 April 2018: School places in England: applications, allocations and appeals

Background: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice. Methods: We examined changes in dynorphin peptide level, prodynorphin mRNA, and substance P mRNA, substance P-immunoreactivity, homeostasis in enzymatic antioxidant system, oxidative parameter, microglial activation, and pro-apoptotic parameter after a neurotoxic dose of MA to clarify the effects of GRe, prodynorphin knockout, pharmacological inhibition of κ-opioid receptor (i.e., nor-binaltorphimine), or neurokinin 1 (NK1) receptor (i.e., L-733,060) against MA insult in mice. Results: GRe attenuated MA-induced decreases in dynorphin level, prodynorphin mRNA expression in the striatum of wild-type (WT) mice. Prodynorphin knockout potentiated MA-induced dopaminergic toxicity in mice. The imbalance of enzymatic antioxidant system, oxidative burdens, microgliosis, and pro-apoptotic changes led to the dopaminergic neurotoxicity. Neuroprotective effects of GRe were more pronounced in prodynorphin knockout than in WT mice. Nor-binaltorphimine, a κ-opioid receptor antagonist, counteracted against protective effects of GRe. In addition, we found that GRe significantly attenuated MA-induced increases in substance P-immunoreactivity and substance P mRNA expression in the substantia nigra. These increases were more evident in prodynorphin knockout than in WT mice. Although, we observed that substance P-immunoreactivity was co-localized in NeuN-immunreactive neurons, GFAP-immunoreactive astrocytes, and Iba-1-immunoreactive microglia. NK1 receptor antagonist L-733,060 or GRe selectively inhibited microgliosis induced by MA. Furthermore, L-733,060 did not show any additive effects against GRe-mediated protective activity (i.e., antioxidant, antimicroglial, and antiapoptotic effects), indicating that NK1 receptor is one of the molecular targets of GRe. Conclusions: Our results suggest that GRe protects MA-induced dopaminergic neurotoxicity via upregulatgion of dynorphin-mediated κ-opioid receptor and downregulation of substance P-mediated NK1 R

Inhibitory effect of positively charged triazine antagonists of prokinecitin receptors on the transient receptor vanilloid type-1 (TRPV1) channel

Four positively charged compounds, previously shown to produce analgesic activity by interacting with prokinecitin receptor or T-type calcium channels, were tested for their ability to inhibit capsaicin-induced elevation of intracellular Ca(2+) elevation in HEK-293 cells stably transfected with the human recombinant TRPV1, with the goal of identifying novel TRPV1 open-pore inhibitors. KYS-05090 showed the highest potency as a TRPV1 antagonist, even higher than that of the open-pore triazine 8aA inhibitor. The latter showed quite remarkable agonist/desensitizer activity at the rat recombinant TRPM8 channel. The activity of KYS-05090 and the other compounds was selective because none of these compounds was able to modulate the rat TRPA1 channel. Open-pore inhibitors of TRPV1 may be a new class of multi-target analgesics with lesser side effects, such as loss of acute pain sensitivity and hyperthermia, than most TRPV1 antagonists developed so far

Differences in complications and asymmetry in patients who did not receive a balancing procedure in two-stage and direct-to-implant breast reconstruction

Background Implant-based immediate breast reconstruction surgery with nipple-sparing mastectomy has recently been favored by patients. However, in patients who do not wish to undergo balancing procedures, it is difficult to select the appropriate implant size, making it challenging to achieve a symmetrical breast shape. Therefore, this study investigated the differences in breast asymmetry and other complications in patients who underwent a two-stage procedure or direct-to-implant (DTI) breast reconstruction to determine whether the two-stage procedure can produce more favorable outcomes. Methods The participants of this study were patients who underwent immediate two-stage breast reconstruction or DTI breast reconstruction from May 2018 to April 2022, did not receive postoperative radiotherapy, and did not wish to undergo any balancing procedures. An acellular dermal matrix was used for breast reconstruction in all patients, and a single reconstructive surgeon performed all the operations. Statistical significance was set at P<0.05. Results No significant differences in complications were found between the patients who underwent DTI breast reconstruction and those who underwent two-stage breast reconstruction. In the two-stage breast reconstruction group, breast volume asymmetry was observed in 18.4% (seven patients), which was significantly lower than the percentage of 44.7% (17 patients) observed in the DTI group. Conclusions Breast asymmetry was observed in a significant proportion of the patients in both groups. However, because breast volume asymmetry was more common in the DTI group than in the two-stage breast reconstruction group, two-stage breast reconstruction may be a favorable method for patients who do not wish to undergo balancing procedures

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

BACKGROUND: There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN: The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION: This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION: Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803)

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

BACKGROUND: Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. METHODS: A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. RESULTS: Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. CONCLUSION: The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. TRIAL REGISTRATION: ClinicalTrials.gov: http://NCT0163425

Increased sFlt-1 to PlGF Ratio in Women Who Subsequently Develop Preeclampsia

The purpose of this study was to determine whether the levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia. We performed a case-control study to compare the levels of sFlt-1 and PlGF in the preeclamptic (n=46) and normal pregnant women (n=100). The maternal plasma levels of sFlt-1 and PlGF were measured by enzyme-linked immunosorbent assay. The sFlt-1 levels were significantly higher in the preeclamptic women than in normal controls (p<0.001), while the PlGF levels were significantly lower (p<0.001). In normal controls, sFlt-1 levels were positively correlated (r=0.27, p=0.008), whereas, in the preeclamptic women, those were negatively correlated with the PlGF levels (r=-0.423, p=0.005). Furthermore, the log[sFlt-1/PlGF] ratio was significantly higher in the preeclamptic women than in normal controls (p<0.001). The receiver operating characteristic curve revealed a specificity of 78% with a diagnostic sensitivity of 80.4%; the optimal cut-off value of the log[sFlt-1/PlGF] ratio was 1.4 (95% CI 0.756-0.910, p<0.001). Preeclampsia showed a strong association with increased levels of sFlt-1 and decreased levels of PlGF in the second trimester maternal plasma. Accordingly, the sFlt-1/PlGF ratio may provide early prediction of subsequent development of preeclampsia

Perinatal Outcome in Twin Pregnancies Complicated by Gestational Diabetes Mellitus: A Comparative Study

The purpose of this study is to compare perinatal outcomes of twin pregnancies complicated by gestational diabetes (GDM) with those unaffected by GDM. A total of 1,154 twin pregnancies who delivered at Cheil General Hospital, between January 1998 and December 2002 were recruited to participate in a retrospective analysis. Out of these twin pregnancies, 37 women were had GDM. Four pregnancies exposed to GDM were excluded due to the loss of medical records; therefore 33 twin pregnancies exposed to GDM were enrolled. We matched the GDM pregnancies with pregnancies unaffected by GDM in a 1:2 ratio; therefore there were 33 GDM/66 without GDM who delivered during the study period. Our findings show that there were no significant differences including birth weight, Apgar score, respiratory distress syndrome, meconium aspiration pneumonia, transient tachypnea of new born, hyperbilirubinemia, hypoglycemia, hypocalcemia and congenital anomalies. Therefore, well controlled GDM may not increase perinatal complications in twin pregnancies. Careful pregnancy management and fetal surveillance in twin pregnancies is important to decrease perinatal complications and maintain a sound pregnancy and healthy offspring