Natural products - Dawn of keloid treatment.

Keloids are prevalent pathological scars, often leading to cosmetic deformities and hindering joint mobility.They cause discomfort, including burning and itching, while gradually expanding and potentially posing a risk of cancer.Developing effective drugs and treatments for keloids has been a persistent challenge in the medical field. Natural products are an important source of innovative drugs and a breakthrough for many knotty disease.Herein, keywords of "natural, plant, compound, extract" were combined with "keloid" and searched in PubMed and Google Scholar, respectively. A total of 32 natural products as well as 9 extracts possessing the potential for treating keloids were ultimately identified.Current research in this field faces a significant challenge due to the lack of suitable animal models, resulting in a predominant reliance on in vitro studies.In vivo and clinical studies are notably scarce as a result.Moreover, there is a notable deficiency in research focusing on the role of nutrients in keloid formation and treatment.The appropriate dosage form (oral, topical, injectable) is crucial for the development of natural product drugs. Finally, the conclusion was hereby made that natural products, when used as adjuncts to other treatments, hold significant potential in the management of keloids.By summarizing the natural products and elucidating their mechanisms in keloid treatment, the present study aims to stimulate further discoveries and research in drug development for effectively addressing this challenging condition.

Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses.

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).

The role of gut microbiota in intestinal disease: from an oxidative stress perspective.

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn's disease. The level of reactive oxygen species (ROS) has been reported to increase when the gut microbiota is dysregulated, especially when several gut bacterial metabolites are present. Although healthy gut microbiota plays a vital role in defending against excessive oxidative stress, intestinal disease is significantly influenced by excessive ROS, and this process is controlled by gut microbiota-mediated immunological responses, DNA damage, and intestinal inflammation. In this review, we discuss the relationship between gut microbiota and intestinal disease from an oxidative stress perspective. In addition, we also provide a summary of the most recent therapeutic approaches for preventing or treating intestinal diseases by modifying gut microbiota.

Silk Nanofibril-Palygorskite Composite Membranes for Efficient Removal of Anionic Dyes.

To develop membrane materials with good performance for water purification that are green and low cost, this work reports an organic-inorganic composite membrane composed of silk nanofibrils (SNFs) and palygorskite (PGS). To improve the stability of the the composite membrane, genipin was used as a crosslinking agent to induce the conformational transition of SNF chains from random coils to ß-sheets, reducing the swelling and hydrolysis of the membrane. The separation performance can be adjusted by tailoring the component ratio of the nanomaterial. The results showed that these membranes can effectively remove anionic dyes from water, and they exhibit excellent water permeability. The SNF-based membrane had strong mechanical and separation properties, and the PGS could tune the structure of composite membranes to enhance their permeability, so this green composite membrane has good prospects in water treatment and purification applications.

Policy Implementation Inconsistency and Emission Leakage: Evidence from The Closure of Polluting Firms.

Public policies often fail to address the unintended behavior of regulated firms and are therefore inconsistent in their implementation, resulting in ineffectiveness. In the process of environmental policy, policy implementation inconsistencies also exist, which is known as emission leakage. Existing studies on the topic focus more on spatial dimension and less attention to time dimension. The reasons for emission leakage over time are two: regulatory laxness and inefficiencies. In this study, we examine whether emission leakage occurs during enterprises' end-of-life cycles. Based on unique high-frequency facility-level monitoring data, we construct a difference-in-differences (DID) model to investigate differences in environmental performance between hazardous chemical production firms in the process of closing and those in the same industry within 20 kilometers. This study finds no emission leakage problem in the processes of relocation and closure, and the concentration of chemical oxygen demand (COD) discharged declines by 28.53 percent. This result is mainly due to top-down regulatory requirements. Nevertheless, policymakers should remain aware of emission leakage when formulating environmental policies and create more substantial supervision to prevent potential leakage.

In situ gelation of aqueous sulfuric acid solution for fuel cells.

Aqueous sulfuric acid solution is a versatile liquid electrolyte for electrochemical applications and gelation of it has the advantages of easy shaping and reduced leaking. Herein, aqueous sulfuric acid solutions with concentrations of 1-4 mol L-1 are fabricated into gel membranes by in situ polymerization of acrylamide as a monomer and divilynbenzene as a crosslinker for fuel cell applications. The gel membrane with an acid concentration of 3.5 mol L-1 exhibited the maximum proton conductivity of 184 mS cm-1 at 30 °C. Tensile fracture strength of the gel membrane reached 53 kPa with a tensile strain of 14. Thermogravimetric analysis reveals that the gel membranes are thermally stable at temperatures up to 231 °C. The gel membranes are successfully assembled into fuel cells and a peak power density of 74 mW cm-2 is achieved. The fuel cell maintains steady operation over 200 h. In situ gelation of aqueous sulfuric acid solution offers an efficient strategy to prepare gel electrolytes for electrochemical devices.

Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy.

CD8+ T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance. Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes. Unfortunately, only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity. Antitumor immunity depends on the activation of the cGAS-STING pathway, as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells (DCs) to activate CD8+ T cells. STING agonists also enhance natural killer (NK) cells to mediate the clearance of CD8+ T cell-resistant tumors. Therefore STING agonists have been intensively sought after. We previously discovered that manganese (Mn) is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING. Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors. Mn-insufficient mice had significantly enhanced tumor growth and metastasis, with greatly reduced tumor-infiltrating CD8+ T cells. Mechanically, Mn2+ promoted DC and macrophage maturation and tumor-specific antigen presentation, augmented CD8+ T cell differentiation, activation and NK cell activation, and increased memory CD8+ T cells. Combining Mn2+ with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice. Importantly, a completed phase 1 clinical trial with the combined regimen of Mn2+ and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors. We propose that this combination strategy warrants further clinical translation.

[Efficacy and mechanism of acupuncture combined with Tongxieyaofang for diarrhea-type irritable bowel syndrome of liver depression and spleen deficiency].

OBJECTIVE: To observe the clinical effect of acupuncture at lower-he acupoints and front-mu acupoints combined with Tongxieyaofang (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism. METHODS: A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared. RESULTS: After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (P<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (P<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (P<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (P<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (P<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (P<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (P<0.05). CONCLUSION: The acupuncture at lower-he acupoints and front-mu acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.

DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B.

Autophagosome and lysosome fusion is an important macroautophagy/autophagy process for cargo degradation, and SNARE proteins, including STX17, SNAP29, VAMP7 and VAMP8, are key players in this process. However, the manner in which this process is precisely regulated is poorly understood. Here, we show that VAMP7B, a SNARE domain-disrupted isoform of R-SNARE protein VAMP7, competes with SNARE domain functional isoform VAMP7A to bind to STX17 and inhibits autophagosome-lysosome fusion. Moreover, we show that DIPK2A, a late endosome- and lysosome-localized protein, binds to VAMP7B, which inhibits the interaction of VAMP7B with STX17 and enhances the binding of STX17 to VAMP7A, thus enhancing autophagosome-lysosome fusion. Furthermore, DIPK2A participates in autophagic degradation of mitochondria proteins and alleviates apoptosis. Thus, we reveal a new aspect of autophagosome-lysosome fusion in which different isoforms of VAMP7 compete with STX17 and their regulation by DIPK2A.Abbreviations: DIPK2A: divergent protein kinase domain 2A; EEA1: early endosome antigen 1; GOLGA2: golgin A2; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MFN2: mitofusin 2; MT-CO2: mitochondrially encoded cytochrome c oxidase II; PARP1: poly(ADP-ribose) polymerase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RAB5A: RAB5A, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; REEP: receptor accessory protein; RTN4: reticulon 4; SNARE: SNAP receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TOMM20: translocase of outer mitochondrial membrane 20; VAMP7: vesicle associated membrane protein 7; VAMP8: vesicle associated membrane protein 8.

Robust Granger Analysis in Lp Norm Space for Directed EEG Network Analysis.

Granger analysis (GA) is widely used to construct directed brain networks based on various physiological recordings, such as functional magnetic resonance imaging, and electroencephalogram (EEG). However, in real applications, EEGs are inevitably contaminated by unexpected artifacts that may distort the networks because of the L2 norm structure utilized in GAs when estimating directed links. Compared with the L2 norm, the Lp ( ) norm can compress outlier effects. In this paper, an extended GA is constructed by applying the Lp ( ) norm strategy to estimate robust causalities under outlier conditions, and a feasible iteration procedure is utilized to solve the new GA model. A quantitative evaluation using a predefined simulation network demonstrates smaller bias errors and higher linkage consistence for the Lp ( , 0.8, 0.6, 0.4, 0.2) -GAs compared with both the Lasso- and L2-GAs under various simulated outlier conditions. Applications in resting-state EEGs that contain ocular artifacts also show that the proposed GA can effectively compress the ocular outlier influence and recover the reliable networks. The proposed Lp-GA may be helpful in capturing the reliable network structure when EEGs are contaminated with artifacts in related studies.

[Effect of Modified Danggui Yinzi on Delayed Allergy in Model Mice with Qi-Blood Deficiency Syndrome].

OBJECTIVE: To explore the effect of Danggui Yinzi (DY) on delayed allergy in model mice with qi-blood deficiency syndrome (QBDS). METHODS: QBDS model was established in 48 Kuming mice of SPF grade by using reserpine and acetophenone hydrazine. Forty of them were then randomly divided into the model group, the loratadine group, the high dose DY group, the middle dose DY group, and the low dose DY group, 8 in each group. Another 8 in line with the same standard were recruited as a blank group. Mice in high, middle, and low dose DY groups were administered with DY concentrated solution at 60, 30, 15 g/kg by gastrogavage. Mice in the loratadine group were administered with loratadine solution at 1.66 mg/kg by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank group by gastrogavage. All medication was given once per day for 1 successive week. Except those in the blank group, the rest mice were evenly smeared with 1% DNCB solution on the abdomen. Five days after skin allergy, 1% DNCB solution was smeared to right ear of all mice to stimulate allergic reaction. Mice in the blank group were smeared in the same way without allergenic reaction. The auricle swelling and the inhibition ratio were determined at 24 h after attack. Blood was collected from orbit and serum IgE level detected using double-antibody sandwich ELISA. RESULTS: Compared with the blank group, auricle swelling obviously increased and serum IgE level was obviously elevated in the model group (P < 0.01). Compared with the model group, auricle swelling obviously decreased and serum IgE level was obviously reduced in the 3 dose DY groups (P < 0.05, P < 0.01). Meanwhile, the auricle swelling degree was superior in high and middle dose DY groups to that in the loratadine group (P < 0.05). The inhibition ratio of auricle swelling was sequenced from high to low as 67.3% in the high dose DY group, 56.0% in the middle dose DY group, 48.1% in the low dose DY group, 47.3% in the loratadine group. CONCLUSIONS: DY could inhibit auricle swelling and lower serum IgE level. It also could inhibit delayed allergic reaction in model mice with QBDS to some extent.

miR-133a enhances the sensitivity of Hep-2 cells and vincristine-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.

The expression levels of the copper transporter P-type adenosine triphosphatase (ATP7B) are known correlate with tumor cell sensitivity to cisplatin. However, the mechanisms underlying cisplatin resistance remained poorly understood. Therefore, in the present study, we treated Hep-2 cells and in-house-developed vincristine-resistant Hep-2v cells with 50, 100, or 200 µM cisplatin and assessed cell viability after 24 or 48 h. Hep-2v cells were shown to be resistant to 50-200 µM cisplatin. Furthermore, using immunofluorescence staining and western blot analysis, we noted that ATP7B, but not copper-transporting ATPase 1 (ATP7A), expression was significantly increased in Hep-2v cells, and this increase was maintained at a higher level compared with Hep-2 cells. As ATP7B is a target of microRNA 133a (miR­133a), the ability of miR­133a to influence cisplatin sensitivity in Hep-2v cells was then assessed by CCK-8 assay. We noted that miR­133a expression was lower in both Hep-2 and Hep-2v cells compared with epithelial NP69 cells. Following treatment with 50 µM cisplatin, in Hep-2v cells expressing exogenous miR­133a we noted reduced ATP7B expression, and these cells had a significantly lower survival rate compared with the control. The present study demonstrates that miR­133a enhances the sensitivity of multidrug-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.

Resection of a laryngeal hemangioma in an adult using an ultrasonic scalpel: A case report.

Adult laryngeal hemangioma is an extremely rare and slowly progressing vascular tumor. The present study describes the first reported case of a male with a large laryngeal hemangioma that was treated by ultrasonic scalpel. A 61-year-old male presented to our hospital with a recurrent pharyngeal foreign body sensation, without hoarseness, hemoptysis, expectoration or dyspnea. A blue-black mass was detected in the right pyriform sinus, with a morular surface and a wide pedicle positioned lateral to the right arytenoid cartilage and aryepiglottic fold under electronic laryngoscopy. Following tracheotomy under local anesthesia, right superior laryngeal artery ligation and laryngeal hemangioma resection via a lateral neck hypopharyngeal approach were performed under general anesthesia using an ultrasonic scalpel. Pathological examination verified that the tumor was a cavernous hemangioma. On day 11, subsequent to post-operative anti-inflammatory and symptomatic treatment, electronic laryngoscopy showed that the arytenoid mucosal edema had decreased and that the movement of the arytenoid was good. There was no recurrence of hemangioma during a 2-year follow-up period. Therefore, it is recommended that complete surgical resection using an ultrasonic scalpel should be considered for similar cases involving large laryngeal hemangiomas.

Autoregressive model in the Lp norm space for EEG analysis.

The autoregressive (AR) model is widely used in electroencephalogram (EEG) analyses such as waveform fitting, spectrum estimation, and system identification. In real applications, EEGs are inevitably contaminated with unexpected outlier artifacts, and this must be overcome. However, most of the current AR models are based on the L2 norm structure, which exaggerates the outlier effect due to the square property of the L2 norm. In this paper, a novel AR object function is constructed in the Lp (p≤1) norm space with the aim to compress the outlier effects on EEG analysis, and a fast iteration procedure is developed to solve this new AR model. The quantitative evaluation using simulated EEGs with outliers proves that the proposed Lp (p≤1) AR can estimate the AR parameters more robustly than the Yule-Walker, Burg and LS methods, under various simulated outlier conditions. The actual application to the resting EEG recording with ocular artifacts also demonstrates that Lp (p≤1) AR can effectively address the outliers and recover a resting EEG power spectrum that is more consistent with its physiological basis.

[Kartagener syndrome and papillary thyroid carcinoma: an unusual combination].

A case of a papillary thyroid carcinoma in a patient with situs inversus with associated bronchiectasis and chronic sinusitis (Kartagener's syndrome) is reported. A 61-year-old male patient has the symptoms of nasal obstruction. nasal purulent discharge and headache for 2 years. Physical examination: right nasal purulent in right nasal cavity and multiple lychee-like opaque mass in right middle meatus. A nodule, one centimeter in diameter, locates in the upper pole of right thyroid. Evidence of full situs inversus viscerum can be confirmmed by chest radiographs and ultrasound doppler. Pathology: right nasal polyps, the right small papillary thyroid cancer. TEM Tip primary ciliary dyskinesia. Clinical diagnosis: Kartagener syndrome, papillary thyroid carcinoma (T1a N0 M0, I period), chronic sinusitis-nasal polyps.