Mechanisms of action of Lycium barbarum polysaccharide in protecting against vitiligo mice through modulation of the STAT3-Hsp70-CXCL9/CXCL10 pathway.

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

Meta-analysis of the efficacy of adding platelet-rich plasma to 308-nm excimer laser for patients with vitiligo.

OBJECTIVE: Platelet-rich plasma (PRP) is a novel treatment option for vitiligo. PRP has been reported to be effective in combination with 308-nm excimer laser therapy, but there is no consensus on their combination use. Therefore, this meta-analysis assessed the efficacy and safety of the combination regimen in patients with vitiligo compared with laser therapy alone. METHODS: The meta-analysis was performed by searching PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang to identify relevant publications published through 1 February 2022. RESULTS: Six studies involving 302 patients were included. Compared with phototherapy alone, combination treatment with PRP and 308-nm excimer laser therapy significantly improved the total response rate and reduced the no response rate. Additionally, the proportions of patients with repigmentation rates of ≥75%, ≥50%, and ≥25% were significantly higher in the combination group than in the monotherapy group. In addition, the rates of adverse events for combination therapy were comparable to those for laser therapy alone, and the recurrence rates were low. CONCLUSIONS: This meta-analysis provided evidence supporting the combined use of PRP and 308-nm excimer laser therapy as a valuable treatment modality for patients with vitiligo based on its superiority to monotherapy.

Lycium barbarum polysaccharide promotes proliferation of human melanocytes via activating the Nrf2/p62 signaling pathway by inducing autophagy in vitro.

Vitiligo is a skin disease characterized by lack of functional melanocytes. Lycium barbarum polysaccharide (LBP) has been demonstrated to preserve keratinocytes and fibroblasts against oxidative stress. This study aimed to explore the efficacy and underlying mechanisms of LBP on autophagy in H2 O2 -damaged human melanocytes. Cellular viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin V-fluorescein isothiocyanate/propidium iodide double staining. Reverse transcription-polymerase chain reaction, western blotting and electron microscopy were performed to detect autophagy. The protein expression level of Nrf2 and p62 were assessed by western blotting. Plasmid transfection and lentiviral infection were used to overexpress and silence Nrf2 in PIG1 cells. LBP promoted the proliferation and inhibited apoptosis of H2 O2 -damaged PIG1 cells. LBP increased the proliferation of H2 O2 -damaged PIG1 cells via induction of autophagy, and Nrf2 shRNA experiment confirmed that LBP activated the Nrf2/p62 signal pathway. These results suggest that LBP may be used for the treatment of vitiligo. PRACTICAL APPLICATIONS: Goji berry is the mature and dried fruit of Lycium barbarum L., which is a common food with a long history in China, as well as a Traditional Chinese Medicine. Our previous research found that LBP could activated the Nrf2/ARE pathway in an ultraviolet (UV)-induced photodamage model of keratinocytes, and increase the levels of phase II detoxification and antioxidant enzymes. We firstly confirmed the anti-vitiligo effects of L. barbarum polysaccharide (LBP) by inducing autophagy and promoted proliferation of human melanocytes, and LBP induced autophagy via activating the Nrf2/p62 signaling pathway in this study. These results proved that LBP can be an effective therapy for vitiligo treatment.

Green Tea Polyphenols Cause Apoptosis and Autophagy in HPV-16 Subgene-Immortalized Human Cervical Epithelial Cells via the Activation of the Nrf2 Pathway.

Infection with human papillomavirus (HPV) is relatively common and certain high-risk HPV strains can induce epithelial dysplasia, increasing the risk of cervical cancer. Green tea polyphenol (GTP) preparations exhibit diverse anti-inflammatory, antioxidative, and antitumor properties In Vitro and In Vivo. Topical GTP application has been recommended as a treatment for genital warts, but the effect of GTP treatment on HPV infection and HPV-associated cancer remains to be established. The present study aimed to explore the mechanism by which GTP affected HPV type 16 (HPV-16)-positive immortalized human cervical epithelial cells. Survival, apoptosis, and autophagocytosis of these cells following GTP treatment was assessed using CCK-8 assay, flow cytometry, and monodansylcadaverine (MDC) staining. These cells were further transfected with an shRNA specific for Nrf2 to generate stable Nrf2-knockdown cells. The levels of Caspase-3, Bcl-2, Bax, P53, Rb, HPV-16 E6, HPV-16 E7, P62, Beclin1 and LC3B were determined via Western blotting. These analyses revealed that GTP treatment induced autophagy and apoptosis in HPV-16-positive cells, while Nrf2 gene knockdown reversed GTP-induced autophagic and apoptotic effects. Together, these results suggested that GTP could alleviate HPV infection and HPV-associated precancerous lesions In Vitro by regulating the Nrf2 pathway, highlighting the therapeutic potential of GTP in treating HPV infection.

Efficacy of low-fluence 1064 nm Q-switched Nd: YAG laser for the treatment of melasma: A meta-analysis and systematic review.

BACKGROUND: Melasma is considered as a type of acquired facial pigmentary disorder that is challenging to treat. Low-fluence 1064 nm Q-switched Nd: YAG laser (LQSNY) has clinical benefits against melasma; however, there are some disputes. OBJECTIVE: To explore these contentious views, we conducted a meta-analysis and systematic review to evaluate the efficacy and safety of LQSNY monotherapy and combined therapy for the treatment of melasma. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant articles from inception to July 2021. The resulting data were analyzed using the Review Manager 5.3 software. RESULTS: Twelve eligible studies comprising 358 patients were included. No significant differences in melasma area and severity index (MASI) were observed between the LQSNY and drug groups (mean difference (MD):-0.26, 95% confidence interval (CI):-1.16-0.64, p = 0.57). We found that combination therapy with LQSNY and drugs had a greater MASI improvement compared with LQSNY therapy alone (MD: 1.78, 95% CI 0.93-2.63, p < 0.0001); nevertheless, no statistically significant results were found in melanin index (MI) and self-assessment. The melasma improvement was similar when using LQSNY alone and LQSNY combined with other lasers in terms of RMASI (MD 0.05, 95% CI:-0.61, 0.70, p = 0.56). Compared with intense pulsed light (IPL) alone, LQSNY with IPL provided an added benefit for melasma severity (MD:3.23, 95% CI:0.65-5.81, p = 0.01). CONCLUSION: Low-fluence 1064 nm Q-switched Nd: YAG laser can be applied as an alternative treatment for drug intolerance. Combination therapy with LQSNY and drugs or other lasers may have pleasantly surprising efficacy, but numerous studies are still needed to verify this.

Efficacy of NB-UVB as Add-on Therapy to Antihistamine in the Treatment of Chronic Urticaria: A Systematic Review and Meta-analysis.

INTRODUCTION: Narrow-band ultraviolet B (NB-UVB) phototherapy has been used for the treatment of chronic urticaria (CU), but the clinical efficacy of this treatment modality requires further evidence. A systematic review and meta-analysis of randomized clinical trials were conducted to evaluate the efficacy and safety of NB-UVB as add-on therapy in the treatment of CU. METHODS: A literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP and WanFang databases up to October 2020. A total of nine studies involving 713 participants met the inclusion criteria. RESULTS: Two trials showed a significant difference in the Urticaria Activity Score between therapy with NB-UVB + antihistamines and that with antihistamines alone (mean difference 8.23, 95% confidence interval [CI] 5.78-10.68, p < 0.00001). Six trials (563 participants) showed a significant benefit of NB-UVB as add-on therapy to antihistamines in the total effective rate (risk ratio [RR] 1.56, 95% CI 1.39-1.75, p < 0.00001). In terms of adverse events, no statistically significant differences were found for NB-UVB + antihistamines versus antihistamines alone (RR 1.10, 95% CI 0.67-1.79, p = 0.71). Combination therapy of NB-UVB + antihistamines yielded a significantly lower risk of recurrence (RR 0.25, 95% CI 0.14-0.44, p < 0.00001). CONCLUSION: Our meta-analysis suggests that combination therapy of NB-UVB + antihistamines is significantly more effective in treating CU than antihistamines alone.

Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is considered an antioxidant agent. NF-E2-related factor-2 (Nrf2) is an important regulator for protection against UV damage. In this study, we verified the performance of LBP and the correlation between LBP and Nrf2. METHODS: HSF cells were treated with LBP to determine dose and time dependencies. An antioxidant response element (ARE) reporter was designed to monitor the activity of the Nrf2 antioxidant pathway. RESULTS: For HSF cells, the optimal LBP treatment was 300 µg/ml for 3 h. The ARE-reporter assay showed that LBP could increase the robustness of p-Nrf2. Treatments with genistein and LY294002 reduced of nuclear p-Nrf2 after 24 h. LBP increased the level of nuclear Nrf2, which functions by both phosphorylation and nuclear translocation. Silencing Nrf2 led to increased reactive oxygen species (ROS) levels, lower cell viability, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSP-PX) levels. This induced a higher level of lipid peroxide (LPO). However, LBP could decrease the levels of ROS and LPO and enhance the levels of SOD and GSP-PX. CONCLUSION: LBP protects HSF cells against UV damage via the regulation of Nrf2.

Lycium barbarum polysaccharide protects human keratinocytes against UVB-induced photo-damage.

Ultraviolet B (UVB) irradiation plays a key role in skin damage, which induces oxidative and inflammatory damages, thereby causing photoaging or photocarcinogenesis. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses significant antioxidative and anti-inflammatory effects on multiple tissues. In the present study, the photoprotective effects and potential underlying molecular mechanisms of LBP against UVB-induced photo-damage were investigated in immortalized human keratinocytes (HaCaT cells). The data indicated that pretreatment with LBP significantly attenuated UVB-induced decrease in cell viability, increase in ROS production and DNA damage. LBP also significantly suppressed UVB-induced p38 MAPK activation, and subsequently reversed caspase-3 activation and MMP-9 expression. Notably, LBP was found to induce Nrf2 nuclear translocation and increase the expression of Nrf2-dependent ARE target genes. Furthermore, the protective effects of LBP were abolished by siRNA-mediated Nrf2 silencing. These results showed that the antioxidant LBP could partially protect against UVB irradiation-induced photo-damage through activation of Nrf2/ARE pathway, thereby scavenging ROS and reducing DNA damage, and subsequently suppressing UVB-induced p38 MAP pathway. Thus, LBP can be potentially used for skincare against oxidative damage from environmental insults.

Effect of Yiqi Tongyang Decoction () on blood T cell subsets in patients with chronic immune thrombocytopenia.

OBJECTIVE: To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to defifine the mechanism of action of YTD. METHODS: The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flflow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control. T-box expressed in T-cells (T-bet) and GATA binding protein 3 (GATA-3) mRNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction. RESULTS: The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy (P<0.05). Th1 cell numbers and the Th1/Th2 ratio fell in the treated patients with CITP to approximate the values of the control group (P>0.05). Th17 cell numbers and the Th17/Treg ratio also decreased in the treatment group (P<0.05), but not to the levels of the controls. The number of Treg cells in the peripheral blood of patients with CITP before treatment was lower than that in the control group (P<0.05), but increased after YTD treatment P<0.05), but not to the level of controls. T-bet and GATA-3 mRNA levels in peripheral blood were initially higher in patients before treatment than controls (P<0.05), but decreased after YTD therapy (P<0.05). CONCLUSIONS: Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cells, play important roles in the pathogenesis of CITP. YTD effificiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.

Topical treatment of green tea polyphenols emulsified in carboxymethyl cellulose protects against acute ultraviolet light B-induced photodamage in hairless mice.

Ultraviolet (UV) radiation causes skin injury and inflammation resulting in impaired immune response and increased risk of skin cancer. It has been shown that green tea polyphenols (GTPs) enhanced intracellular antioxidant defense and promoted the downregulation of proapoptotic genes, and they could be used to protect against the damage induced by UV irradiation. However, the high instability and poor bioavailability of GTPs impose restrictions on their potential pharmacological use. Here we show that carboxymethyl cellulose sodium (CMC-Na) had a stabilizing effect on GTPs under aqueous conditions and topical application of GTPs (emulsified in CMC-Na) had a strong photoprotective effect against acute UVB induced photodamage in uncovered (Uncv) hairless mice skin. After 8 h of incubation at 50 °C with CMC-Na, a percentage i.e. 93% of GTPs was preserved, while in the absence of CMC-Na, a percentage of only 61% was preserved. Topical treatment of emulsified GTPs effectively inhibited acute UVB-induced infiltration of inflammatory cells, increase of skin thickness, oxidative stress such as depletion of antioxidant enzymes and lipid oxidation, and induced nuclear accumulation of Nrf2 in the mice skin. We also discovered the ability of GTPs to simultaneously trigger accumulation of nuclear Nrf2 and export of nuclear Bach1. Altogether, our findings reinforced the putative application of GTPs in the prevention/minimization of the deleterious effects of UV on the skin.

A non-additive interaction in a single locus causes a very short root phenotype in wheat.

Non-additive allelic interactions underlie over dominant and under dominant inheritance, which explain positive and negative heterosis. These heteroses are often observed in the aboveground traits, but rarely reported in root. We identified a very short root (VSR) phenotype in the F1 hybrid between the common wheat (Triticum aestivum L.) landrace Chinese Spring and synthetic wheat accession TA4152-71. When germinated in tap water, primary roots of the parental lines reached ~15 cm 10 days after germination, but those of the F1 hybrid were ~3 cm long. Selfing populations segregated at a 1 (long-root) to 1 (short-root) ratio, indicating that VSR is controlled by a non-additive interaction between two alleles in a single gene locus, designated as Vsr1. Genome mapping localized the Vsr1 locus in a 3.8-cM interval delimited by markers XWL954 and XWL2506 on chromosome arm 5DL. When planted in vermiculite with supplemental fertilizer, the F1 hybrid had normal root growth, virtually identical to the parental lines, but the advanced backcrossing populations segregated for VSR, indicating that the F1 VSR expression was suppressed by interactions between other genes in the parental background and the vermiculite conditions. Preliminary physiological analyses showed that the VSR suppression is independent of light status but related to potassium homeostasis. Phenotyping additional hybrids between common wheat and synthetics revealed a high VSR frequency and their segregation data suggested more Vsr loci involved. Because the VSR plants can be regularly maintained and readily phenotyped at the early developmental stage, it provides a model for studies of non-additive interactions in wheat.