Simple Method for Preparing Starch Inclusion Complexes with Enhanced Amylolysis Resistance and Antioxidant Properties.

Slow-digesting starch with bioactive functionality has been attracting much interest with the increasing incidence of type-2 diabetes and other diet-related illnesses. The present study demonstrates a simple method for preparing a starch inclusion complex with reduced enzymic digestion and enhanced antioxidant activities using debranched pea starch (PS) and 10-gingerol (10G). Enzymically debranched starch complexed more 10G and formed more structurally ordered starch-10G complexes compared to PS that had not been debranched. Debranching for 6 h resulted in starch with better complexing ability for 10G than starches debranched for longer times. The debranched starch-10G complexes had higher antioxidant activities and a much slower in vitro enzymic digestion profile (rate and hydrolysis extent) than the 10G complex prepared with starch that was not debranched. Our study demonstrates that debranched pea starch-10G complexes with slow-digesting and antioxidant properties are likely to be of interest for developing ingredients for healthier food choices.

Novel Type of Slowly Digested Starch Complex with Antioxidant Properties.

With the increasing number of diabetic patients in the world, there is an urgent requirement to reduce the incidence of diabetes. It is considered that a viable prophylactic treatment for type 2 diabetes mellitus is to reduce starch digestibility and oxidative stress. In this study, a novel type of slowly digested starch [pea starch (PS)-gingerol complex] was fabricated to evaluate its in vitro enzymatic digestibility and antioxidant activities. Theoretical and experimental analyses showed that PS can encapsulate gingerols with long alkyl chains to form starch-gingerol complexes, which are further stacked into a mixture of V6- and V7-crystallites. These complexes, in particular the PS-10-gingerol complex, showed high resistance to amylolysis and good antioxidant activities. This study demonstrates that these novel starch-gingerol complexes have the potential to deliver antioxidants encapsulated in starch with slow-digesting properties and reduce oxidative stress. Moreover, this new type of slowly digested starch with antioxidant properties showed great potential in the prevention of type 2 diabetes.

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.

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.

Split-face comparison of the efficacy of picosecond 532 nm Nd:YAG laser and Q-switched 755 nm Alexandrite laser for treatment of freckles.

To date, there has been little study of comparison between picosecond 532 nm laser and 755 nm Q-switched Alexandrite lasers in the treatment of freckles. To evaluate the efficacy and safety of picosecond 532 nm laser (PS 532) and 755 nm Q-switched Alexandrite laser (QSAL) for treatment of freckles in a split-face manner. Eighteen patients with freckles were enrolled in the study. The right and left sides of their faces were randomly assigned to either a QSAL-treated group or PS 532-treated group. The degree of pain, satisfaction with the results, and adverse events associated with the laser treatment were evaluated using a questionnaire. All of the patients were followed up at 4 and 12 weeks after one treatment session. Among the 18 patients, PS 532 was found to be associated with less pain (3.56 ± 2.431) than QSAL (3.94 ± 1.893), but the difference was not statistically significant. The curative effect and satisfaction associated with 755 nm Q-switched Alexandrite laser was greater than that of picosecond 532 nm laser (P < .001). Both picosecond 532 nm laser and QSAL are effective in the treatment of freckles, and QSAL has a greater rate of satisfaction and curative effect.

Effects of tea polyphenols on UVA-induced melanogenesis via inhibition of α-MSH-MC1R signalling pathway.

Introduction: Ultraviolet (UV) irradiation is a major environmental factor affecting photoaging, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the melanogenesis progress, UV is thought to play a major role in tanning. The pathway of α-melanocyte-stimulating hormone (α-MSH)-melanocortin receptor 1 (MC1R) is associated with UV-induced melanogenesis. Thus, α-MSH antagonists may have applications in the prevention of melanogenesis. Aim: To investigate the effects of tea polyphenols (TPS) on pigmentation, and further explore the underlying mechanism. Material and methods: Human keratinocyte cell line (HaCaT) cells and Human epidermal melanocytes (HEM) were exposed to UVA and treated with different concentrations of TPS or Nonapeptide-1 acetate salt (N-1A). Then, cell viability, melanin content, and tyrosinase activity of both kinds of cells were detected. Quantification of α-MSH in HaCaT cells and HEM cells determined by ELISA assays. Immunohistochemistry of HEM cells was employed to further investigate the expression of melanogenesis-related proteins. Results: The different concentrations of TPS were found to decrease the melanin content, tyrosinase activity and melanogenesis-related proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)1, and TRP2. Besides, TPS inhibited α-MSH-MC1R signalling through directly suppressed α-MSH expression rather than the down-regulated expression level of MC1R. Conclusions: Our findings indicate that TPS may be a potential whitening agent for use in cosmetics and the medical treatment of hyperpigmentation disorders.

CRISPR/Cas9-mediated targeted T-DNA integration in rice.

KEY MESSAGE: Combining with a CRISPR/Cas9 system, Agrobacterium-mediated transformation can lead to precise targeted T-DNA integration in the rice genome. Agrobacterium-mediated T-DNA integration into the plant genomes is random, which often causes variable transgene expression and insertional mutagenesis. Because T-DNA preferentially integrates into double-strand DNA breaks, we adapted a CRISPR/Cas9 system to demonstrate that targeted T-DNA integration can be achieved in the rice genome. Using a standard Agrobacterium binary vector, we constructed a T-DNA that contains a CRISPR/Cas9 system using SpCas9 and a gRNA targeting the exon of the rice AP2 domain-containing protein gene Os01g04020. The T-DNA also carried a red fluorescent protein and a hygromycin resistance (hptII) gene. One version of the vector had hptII expression driven by an OsAct2 promoter. In an effort to detect targeted T-DNA insertion events, we built another T-DNA with a promoterless hptII gene adjacent to the T-DNA right border such that integration of T-DNA into the targeted exon sequence in-frame with the hptII gene would allow hptII expression. Our results showed that these constructs could produce targeted T-DNA insertions with frequencies ranging between 4 and 5.3% of transgenic callus events, in addition to generating a high frequency (50-80%) of targeted indel mutations. Sequencing analyses showed that four out of five sequenced T-DNA/gDNA junctions carry a single copy of full-length T-DNA at the target site. Our results indicate that Agrobacterium-mediated transformation combined with a CRISPR/Cas9 system can efficiently generate targeted T-DNA insertions.

Modulation effect of vaginal mucosal microflora and susceptibility to Neisseria gonorrhoeae infections: a systematic review and meta-analysis.

OBJECTIVE: The vaginal microbiota may modulate susceptibility to Neisseria gonorrhea (NG) infections. The objective of this meta-analysis was to evaluate the association between these NG infections and the vaginal microbiota. METHOD: A systematic review and meta-analysis was conducted to investigate the correlation of vaginal microbiota and NG risk. Primary sources of the reviewed studies were from inception through December 2018. Vaginal mucosa microflora were dichotomized into high-Lactobacillus vaginal microbiota and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or 16S rRNA gene sequencing. RESULTS: A total of 8 studies qualified for inclusion in this meta-analysis. LL-VMB could be regarded as worse prognostic factor, and the pooled OR was 1.33 (95% CI 1.02, 1.73; P = 0.04, I2 = 44%). LL-VMB was associated with a significantly higher susceptibility of NG. Trend for the sensitive analysis was consistence with the primary outcome. Significant publication bias was not detected by the funnel plot. CONCLUSION: In conclusion, the systematic review and meta-analysis has demonstrated that LL-VMB was significantly associated with a high NG susceptibility.

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.

Pterostilbene's protective effects against photodamage caused by UVA/UVB irradiation.

Aim: The aim of this study was to further elucidate the mechanism of pterostilbene against UVA/UVB irradiation and the Nuclear factor E2-related factor 2 (Nrf2) signal pathway. Methods: A photo-damage model with UVA/UVB irradiation in HaCat cells was established and used in this study. The dose of pterostilbene was selected through MTS assay. Cell proliferation and apoptosis in Nrf2 and knockdown Nrf2 cells was detected by MTS assay. Expression of CAT, HO-1, and SOD in Nrf2 and knockdown Nrf2 cells was explored by qPCR. Western blot was used to analysis of Nrf2 nuclear translocation changes in Nrf2 and knockdown Nrf2 cells. Protein carbonyl content and MDA content was tested. Results: Our photo-damage model was successfully established and 20J/cm² UVA and 57mJ/cm² UVB irradiation was the suitable dose for HaCaT cell damage study. UVA/UVB irradiation would affect Nrf2 protein location, especial for 9.75 µM pterostilbene dose. In addition, cell proliferation could be significantly inhibited by UVA/UVB treatments (P<0.05), whereas, 9.75 µM pterostilbene treatment can alleviate the photo-damage. UVA/UVB irradiation would lead to decreased expressions of CAT, HO-1, and SOD. Carbonyl content and MDA was significantly changed by UVA/UVB treatments (P<0.05). The adverse events could be reversed by adding 9.75 µM pterostilbene. Western blot analysis showed that Nrf2 cytoplasm content in UVA/UVB treated cells was reduced and Nrf2 nuclear content was increased, which are different with the normal HaCaT cells without knockdown Nrf2 treatment (P<0.05). The results of cell proliferation, apoptosis, and cell antioxidant capacity in knockdown Nrf2 treated HaCaT cells were also significantly different with the normal HaCaT cells without knockdown Nrf2 treatment (P<0.05). Conclusion: We hypothesize that pterostilbene could play an anti-oxidation role via the Nrf2 signal pathway.

AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo.

Recent studies suggest that forced activation of AMP-activated protein kinase (AMPK) could inhibit melanoma cell proliferation. In this report, we evaluated the anti-melanoma cell activity by a novel small-molecular AMPK activator, GSK621. Treatment of GSK621 decreased survival and proliferation of human melanoma cells (A375, WM-115 and SK-Mel-2 lines), which was accompanied by activation of caspase-3/-9 and apoptosis. Reversely, caspase inhibitors attenuated GSK621-induced cytotoxicity against melanoma cells. Significantly, GSK621 was more potent than other AMPK activators (A769662, Compound 13 and AICAR) in inhibiting melanoma cells. Intriguingly, same GSK621 treatment was non-cytotoxic or pro-apoptotic against human melanocytes. Molecularly, we showed that activation of AMPK mediated GSK621's activity against melanoma cells. AMPKα1 shRNA knockdown or dominant negative mutation (T172A) dramatically attenuated GSK621-induced melanoma cell lethality. Further studies revealed that MEK-ERK activation might be the primary resistance factor of GSK621. MEK-ERK inhibition, either genetically or pharmacologically, significantly sensitized melanoma cells to GSK-621. Remarkably, intraperitoneal (i.p.) injection of GSK621 inhibited A375 tumor growth in SCID mice. Co-administration of MEK-ERK inhibitor MEK162 further sensitized GSK621-induced anti-A375 tumor activity in vivo. Together, the results imply that targeted activation of AMPK by GSK621 inhibits melanoma cell survival and proliferation. MEK-ERK inhibition may further sensitize GSK621's anti-melanoma cell activity in vitro and in vivo.

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.

Hepatitis B virus genotype A: design of reference sequences for sub-genotypes.

Genotype A of hepatitis B virus (HBV/A) is widespread and is currently divided into six sub-genotypes. Suitable reference sequences for different sub-genotypes can facilitate research on HBV/A. However, the current reference sequences for this virus are insufficient. In the present work, we retrieved 442 full-length HBV/A genomic sequences from the GenBank database and classified them into sub-genotypes by phylogenetic analysis. By the maximum likelihood method using the MEGA6.0 software, we established the reference sequences for different HBV/A sub-genotypes. Our analyses demonstrated that these reference sequences clustered phylogenetically with known strains, indicating that the reference sequences we established indeed belonged to the right sub-genotypes. HBV/A subtype sequences were selected by geographic origins and grouped as sub-genotypes including A1-South Africa, A2-Europe, A3-Cameroon, and A5-Haiti. Reference sequences of sub-genotypes A1, A2, A3, and A5 were constructed and deposited into GenBank (KP234050-KP234053). By applying phylogenetic analyses, we further determined the time to most recent common ancestor of HBV/A lineages. In conclusion, these newly established reference sequences can provide suitable reference standards for studies on the molecular biology and virology of HBV genotype A.

Prediction model for sustained hepatitis B e antigen seroconversion to peginterferon alfa-2a in chronic hepatitis B.

BACKGROUND AND AIM: Clinically applicable models to predict hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) response to peginterferon (PEG-IFN) are scarce. This study aimed to develop simple scoring systems, based on multiple parameters, for predicting sustained HBeAg seroconversion to PEG-IFN. METHODS: Eighty-five treatment-naïve patients with HBeAg-positive CHB underwent 52-week PEG-IFN treatment and 24-week follow-up. Logistic regression analysis assessed parameters at baseline and weeks 12, 24, and 52 to predict HBeAg seroconversion at week 24 off-treatment. The best three predictors at each time point were included in prediction models of PEG-IFN therapy efficacy. RESULTS: The three most meaningful predictors were alanine aminotransferase (ALT) > 5 × ULN, HBeAg ≤ 500 S/CO, and antibody to hepatitis B core antigen (anti-HBc) > 10.7 S/CO at baseline; HBeAg ≤ 20 S/CO, anti-HBc > 11.7 S/CO, and HBeAg decline > 1 log10 S/CO at week 12; ALT > 2 × ULN, HBeAg ≤ 15 S/CO, and anti-HBc > 10.4 S/CO at week 24; HBeAg ≤ 5 S/CO, anti-HBc > 11.1 S/CO, and hepatitis B virus DNA decline > 2 log10 copies/mL at week 52. Parameters meeting optimal cutoff thresholds were scored 1 or otherwise scored 0. For total scores of 0 versus 3 at baseline and weeks 12, 24, and 52, response rates were 6.3%, 12.5%, 0%, and 0% versus 90.0%, 83.3%, 76.9%, and 86.4%, respectively. CONCLUSIONS: We successfully established prediction models for PEG-IFN response in HBeAg-positive CHB.

Fine mapping of shattering locus Br2 reveals a putative chromosomal inversion polymorphism between the two lineages of Aegilops tauschii.

KEY MESSAGE: This work laid the foundation for cloning of shattering gene Br2 and provided first line of evidence that two major Aegilops tauschii lineages are differentiated by an inversion polymorphism. Chromosome inversions often accompany population differentiation and capture local adaptation during speciation. Aegilops tauschii, the D-genome donor species of hexaploid wheat, consists of two genetically isolated lineages, L1 and L2, but little is known about the genetic mechanisms underlying the population differentiation in this diploid species. During fine mapping of the shattering gene Br2 using a large F2 population derived from a cross between TA1604 (an L1 accession) and AL8/78 (an L2 accession), we found contrasting patterns of crossover distribution in the Br2 interval and neighboring regions despite the high local gene synteny with Brachypodium distachyon and rice. Br2 was localized in a 0.08-cM interval, and 13 marker loci formed a block, where single-crossovers were completely suppressed, but double-crossovers were enriched with a recombination rate of ~11 cM/Mb. In contrast, in a neighboring region no double-crossover was recovered, but single-crossover rate reached 24 cM/Mb, which is much higher than the genome-wide average. This result suggests a putative inversion polymorphism between the parental lines in the Br2 region. Genotyping using the markers from the Br2 region divided a collection of 55 randomly sampled A. tauschii accessions into two major groups, and they are largely genetically isolated. The two groups correspond to the L1 and L2 lineages based on their geographic distribution patterns. This provides first evidence that inversions may underlie the evolution of A. tauschii lineages. The presence of inter-lineage inversions may complicate map-based cloning in A. tauschii and transfer of useful traits to wheat.

The chloroplast view of the evolution of polyploid wheat.

Polyploid wheats comprise four species: Triticum turgidum (AABB genomes) and T. aestivum (AABBDD) in the Emmer lineage, and T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m) A(m) ) in the Timopheevi lineage. Genetic relationships between chloroplast genomes were studied to trace the evolutionary history of the species. Twenty-five chloroplast genomes were sequenced, and 1127 plant accessions were genotyped, representing 13 Triticum and Aegilops species. The A. speltoides (SS genome) diverged before the divergence of T. urartu (AA), A. tauschii (DD) and the Aegilops species of the Sitopsis section. Aegilops speltoides forms a monophyletic clade with the polyploid Emmer and Timopheevi wheats, which originated within the last 0.7 and 0.4 Myr, respectively. The geographic distribution of chloroplast haplotypes of the wild tetraploid wheats and A. speltoides illustrates the possible geographic origin of the Emmer lineage in the southern Levant and the Timopheevi lineage in northern Iraq. Aegilops speltoides is the closest relative of the diploid donor of the chloroplast (cytoplasm), as well as the B and G genomes to Timopheevi and Emmer lineages. Chloroplast haplotypes were often shared by species or subspecies within major lineages and between the lineages, indicating the contribution of introgression to the evolution and domestication of polyploid wheats.

Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study on Effectiveness, Safety and Predictors of Treatment Outcome.

Background: Although omalizumab has shown success in treating chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines, the exact mechanism of action and predictive markers of response remain unclear. Purpose: The aim of this study was to examine the correlation between baseline levels of biomarkers and clinical parameters with omalizumab response and response rate in patients with CSU. Methods: This retrospective study included 82 adult CSU patients who received omalizumab 300mg every 4 weeks for 16 weeks between January 2022 and December 2023. Treatment response was assessed using UAS7 and DLQI scores at baseline and weeks 4, 8, 12, and 16. Responders were defined as patients achieving UAS7 < 7, with early and late responders categorized based on response within or after 4 weeks, respectively. Baseline clinical features and laboratory biomarkers were compared between responders and non-responders. Results: The overall response rate was 71.95% (59/82), with 23 early responders and 36 late responders. Responders had significantly lower baseline UAS7 (median: 28 vs 35, P < 0.01), DLQI (median: 8 vs 15, P < 0.001), and IL-17 levels (median: 0.53 vs 1.26 pg/mL, P < 0.001) compared to non-responders. Baseline UAS7 > 31, DLQI > 9.5, and IL-17 > 0.775 pg/mL predicted non-response with sensitivities of 78.26%, 100%, and 78.26%, and specificities of 67.8%, 59.32%, and 72.88%, respectively. ASST positivity and comorbid allergic diseases were associated with early response (P < 0.05). Adverse events were reported in 6.09% of patients, including mild injection site reactions and transient urticaria exacerbation, not requiring treatment discontinuation. Conclusion: This study suggests that omalizumab is an effective and safe treatment option for antihistamine-refractory CSU. Baseline UAS7, DLQI, ASST status, serum total IgE levels, and IL-17 may serve as potential predictors of omalizumab response. Notably, ASST positivity and comorbid allergic diseases were associated with an early response to treatment. These findings highlight the importance of considering individual patient characteristics when predicting the likelihood and timing of response to omalizumab in CSU.

Network pharmacology analysis of the Huangqi-Gancao herb pair reveals quercetin as a therapeutics for allergic rhinitis via the RELA-regulated IFNG/IRF1 axis response.

Despite the complexity of allergic rhinitis (AR) pathogenesis, no FDA-approved drug has been developed to achieve optimal therapeutic effects. The present study explored the efficacy and mechanism of Huangqi (Hedysarum Multijugum Maxim)-Gancao (Glycyrrhizae Radix et Rhizoma or licorice) herb pair in treating AR by network pharmacology and experimental approaches. The bioactive ingredients of Huangqi and Gancao were identified and used to predict the targets of these herbs in AR and generate the pharmacological network. Ovalbumin (OVA)-induced AR mouse model was established to assess the anti-AR effect of the Huangqi decoction (HQD) prepared based on both herbs. We identified 90 active ingredients of the Huangqi-Gancao pair, targeting 69 AR-related genes. Quercetin (QUE) was identified as the hub ingredient of this pair, with 57 targets in AR. The protein-protein interaction (PPI) network analysis and molecular docking revealed IL1B, TNF, STAT1, IL6, PTGS2, RELA, IL2, NFKBIA, IFNG, IL10, IL1A, IRF1, EGFR, and CXCL10 as important targets of QUE in AR treatment. Experimentally, QUE or HQD significantly alleviated the AR-induced histopathological changes, AR symptoms, and IgE level and counteracted AR-induced expression changes of IFNG, IRF1, RELA, and NFKBIA. These effects were promoted by the NF-kB inhibitor helenalin, indicating that HQD and QUE counteracted AR in mice by regulating the IFNG/IRF1 signaling via the NF-κB pathway in AR mice. These findings shed light on the efficacy of the constituents of Huangqi-Gancao pair, their potential targets, and the molecular mechanisms of HQD in treating AR, which could advance the development of tailored therapeutic interventions for this disorder.

Combination of high-frequency electrocautery therapy and ALA-PDT in hyperkeratotic vulvar lichen sclerosus: Series of seven cases.

SIGNIFICANCE: ALA-PDT effectively treats Vulvar lichen sclerosus et atrophicus (VLSA), but it requires multiple repetitions for satisfactory results. To enhance efficacy, we employed a combination of high-frequency electrocautery therapy and ALA-PDT in treating seven VLSA patients. APPROACH: Lesions and leukoplakia in the seven women with VLSA were removed using a high-frequency generator. PDT was administered after wound healing, and it was repeated six times. Follow-up assessments were carried out at 1, 3, and 6 months to evaluate the severity of pruritus and investigate lesion repigmentation. RESULTS: Following the combined therapy, the disappearance of pruritus was observed in all patients, and normal color and thickness were restored to their skin. Two patients reported mild pruritus with a score of 2 one month after treatment, which persisted until the 6-month follow-up, while the remaining patients remained free from pruritus. No recurrence of skin lesions was observed in any of the patients. CONCLUSIONS: The combined therapy for the treatment of VLSA is found to be convenient, effective, and easily promotable.