The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy.

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each.

pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

Molecular mechanism of Chang Shen Hua volatile oil modulating brain cAMP-PKA-CREB pathway to improve depression-like behavior in rats.

BACKGROUND: Depression is a common and complex mental illness that manifests as persistent episodes of sadness, loss of interest, and decreased energy, which might lead to self-harm and suicide in severe cases. Reportedly, depression affects 3.8 % of the world's population and has been listed as one of the major global public health concerns. In recent years, aromatherapy has been widely used as an alternative and complementary therapy in the prevention and treatment of depression; people can relieve anxiety and depression by sniffing plant aromatic essential oils. Acorus tatarinowii and Panax ginseng essential oils in Chang Shen Hua volatile oil (CSHVO) are derived from Acorus tatarinowii and Panax ginseng, respectively, the main medicines in the famous Chinese medicine prescription Kai Xin San (KXS), Then, these oils are combined with the essential oil of Albizia julibrissin flower to form a new Chinese medicine inhalation preparation, CSHVO. KXS has been widely used in the treatment of depression; however, whether CSHVO can ameliorate depression-like behavior, its pharmacological effects, and the underlying mechanisms of action are yet to be elucidated. STUDY DESIGN AND METHODS: A rat model of chronic and unpredictable mild stimulation (CUMS) combined with orphan rearing was treated with CSHVO for 4 weeks. Using behavioral tests (sucrose preference, force swimming, tail suspension, and open field), the depression-like degree was evaluated. Concurrently, brain homogenate and serum biochemistry were analyzed to assess the changes in the neurotransmitters and inflammatory and neurotrophic factors. Furthermore, tissue samples were collected for histological and protein analyses. In addition, network pharmacology and molecular docking analyses of the major active compounds, potential therapeutic targets, and intervention pathways predicted a role of CSHVO in depression relief. Subsequently, these predictions were confirmed by in vitro experiments using a corticosterone (CORT)-induced PC12 cell damage model. RESULTS: CSHVO inhalation can effectively improve the weight and depression-like behavior of depressed rats and regulate the expression of inflammatory factors and neurotransmitters. Hematoxylin-eosin, Nissl, and immunofluorescence staining indicated that compared to the model group, the pathological damage to the brain tissues of rats in the CSHVO groups was improved. The network pharmacological analysis revealed that 144 CSHVO active compounds mediate 71 targets relevant to depression treatment, most of which are rich in the cAMP signaling and inflammatory cytokine pathways. Protein-protein interaction analysis showed that TNF, IL6, and AKT are the core anti-depressive targets of CSHVO. Molecular docking analysis showed an adequate binding between the active ingredients and the key targets. In vitro experiments showed that compared to the model group, the survival rate of PC12 cells induced by CSHVO intervention was increased, the apoptosis rate was decreased, and the expression of inflammatory cytokines in the cell supernatant was improved. Western blot analysis and immunofluorescence staining confirmed that CSHVO regulates PC12 cells in the CORT model through the cAMP-PKA-CREB signaling pathway, and pretreatment with PKA blocker H89 eliminates the protective effect of CSHVO on CORT-induced PC12 cells. CONCLUSIONS: CSHVO improves CORT-induced injury in the PC12 cell model and CUMS combined with orphan rearing-induced depression model in rats. The antidepressant mechanism of CSHVO is associated with the modulation of the cAMP-PKA-CREB signaling pathway.

A controllable Y-shaped DNA structure assisted aptasensor for the simultaneous detection of AFB1 and OTA based on ARGET ATRP.

The development of a simple, rapid, and sensitive technology for the simultaneous detection of mycotoxins is of great significance in ensuring the safety of foods and drugs. Herein, a fluorescence aptasensor with high sensitivity and reproducibility for the simultaneous detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA) was developed. In this sensing system, AFB1 and OTA aptamers were co-immobilized on the surface of magnetic beads (MBs) to form a Y-shaped structure through the principle of complementary base pairing, and were used as recognition probes to specifically capture the target. Activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) was used as a signal amplification strategy to improve the sensitivity. The initiator modified at the end of an antibody initiates the ARGET ATRP reaction. Different fluorescence signals were designed to achieve the simultaneous detection of OTA and AFB1 with limits of 426.18 and 79.55 fg mL-1 for AFB1 and OTA, respectively. In addition, experiments were conducted on three types of samples, and the recoveries of the two mycotoxins ranged from 87.30% to 109.50%, with relative standard deviations ranging from 0.50% to 4.92% under reproducible conditions. The results suggest that the developed aptasensor is sufficient to meet the different regulatory requirements of the two mycotoxins in food and drug safety and shows great potential.

Effects of Momordica charantia L. supplementation on glycemic control and lipid profile in type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.

Background and aims: Momordica charantia L. (M. charantia) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM. Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals. Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: -0.85 mmol/L; 95%CI: -1.44, -0.26; p = 0.005; I2 = 73.4 %), postprandial glucose (PPG) (WMD: -2.28 mmol/L; 95%CI: -3.35, -1.21; p = 0.000; I2 = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.38 %; 95%CI: -0.53, -0.23; p = 0.000; I2 = 37.6 %), and total cholesterol (TC) (WMD: -0.38 mmol/L; 95%CI: -0.70, -0.07; p = 0.017; I2 = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results.

In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence.

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

Efficacy and safety of adjuvant topical application of botanicals in the treatment of melasma: A systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy and safety of topical application of botanical (TAB) adjuvants in the treatment of melasma and provide evidence-based medical evidence for their clinical application. Methods: Medline, Web of Science, EMBASE, Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, databases were searched to identify all randomized controlled clinical trials on TAB adjuvant treatment for melasma from inception to May 2023. The primary outcomes included clinical efficacy, adverse effects, recurrence rate, and melanin index. Subgroup analyses were performed using the Melasma Area Severity Index (MASI) scores. Results: This study included 16 randomized trials with 1386 participants. Eligible trials demonstrated that topical phytomedicine adjuvant treatment for melasma increased clinical effectiveness (RR = 1.14, 95% CI (1.10, 1.19), P ＜0.00001), decreased recurrence rate (RR = 0.28, 95% CI (0.13, 0.59), P = 0.0009), and decreased melanin index (MI) (MD = -22.2,95% CI (-31.79, -12.61), P < 0.00001). In addition, subgroup analysis showed that topical phytomedicines reduced MASI scores (I2 = 0%, MDI = -0.95, 95% CI (-1.23,0.67), P < 0.00001), but when scored as the rate of decrease in MASI, topical phytomedicines had high MASI scores (I2 = 15%, MD = 0.3, 95% CI (0, 0.59), P = 0.05), indicating a slower rate of melasma mitigation when botanicals were applied topically. Although burning pain, redness and other mild adverse reactions may occur during the treatment period, they can be recovered on their own, and there is no statistical significance in the comparison of the two groups (RR = 0.95, 95% CI (0.42, 2.51), P = 0.91). Conclusion: TAB for melasma has a clear adjuvant clinical efficacy, a low recurrence rate, and does not cause serious adverse effects. An appropriate administration method may achieve better efficacy; however, this requires further verification.

Network pharmacology and experimental evidence: MAPK signaling pathway is involved in the anti-asthma roles of Perilla frutescens leaf.

Perilla frutescens (PF) leaf is a traditional Chinese medicine and food with beneficial effects on allergic asthma. We sought to elucidate the active compounds, the targets, and underlying mechanisms of PF leaf in the treatment of allergic asthma by using experimental pharmacology and network pharmacology. An OVA-allergic asthma murine model was constructed to evaluate the effect of PF leaf on allergic asthma. And the network pharmacology and western blotting were performed to evaluate its underlying mechanisms in allergic asthma. PF leaf treatment significantly improved the lung function of OVA model mice and mitigated lung injury by significantly reducing of OVA-specific immunoglobulin E in serum, and interleukin 4, interleukin 5 and tumor necrosis factor alpha in the bronchoalveolar lavage fluid. 50 core targets were screened based on 8 compounds (determined by high performance liquid chromatography) through compound-target- disease network. Furthermore, MAPK signaling pathway was identified as the pathway mediated by PF leaf with the most potential against allergic asthma. And the WB results showed that PF leaf could down-regulate the expression of p-ERK, p-JNK and p-p38, which was highly consistent with the predicted targets and pathway network. In conclusion, this study provides the evidence to support the molecular mechanisms of PF leaf on the treatment of allergic asthma using network pharmacology and in vivo experiments.

Platforms of graphene/MXene heterostructure for electrochemical monitoring of rutin in drug and Tartary buckwheat tea.

The use of two-dimensional heterostructure composite as electrode modification material has become a new strategy to improve the electrocatalytic activity and electroactive sites of electrochemical sensor. Herein, a soluble heterostructure, namely rGO-PSS@MXene, was designed and synthesized by integrating poly (sodium p-styrenesulfonate)-functionalized reduced graphene oxide into MXene nanosheets via ultrasonic method. The interactive heterostructure can effectively alleviate the self-stacking of MXene and rGO, endowing them with superior electron transfer capacity and large specific surface area, thereby producing prominent synergistic electrocatalytic effect towards rutin. In addition, the excellent enrichment effect of rGO-PSS@MXene for rutin also plays an important role through the electrostatic and π-π stacking interactions. The electrochemical characteristics of rutin on the sensor were examined in detail and a sensitive sensing method was proposed. Under optimized conditions, the method showed satisfactory linear relationship for rutin in the concentration range of 0.005-10.0 µM, with limit of detection of 1.8 nM (S/N = 3). The quantitative validation results in herbal medicine and commercial Tartary buckwheat tea were highly consistent with the labeled quantity and the results of HPLC determination, respectively, suggesting the sensor possessed excellent selectivity and accuracy. This proposed strategy for rutin determination is expected to expand the application of MXene heterostructure in electrochemical sensors, and is envisioned as a promising candidate for quality monitoring of drugs and foods.

Immunogenicity and safety of ebolavirus vaccines in healthy adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV). METHODS: We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls. RESULTS: Twenty-nine RCTs (n = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28-15.41; I2 = 33%; P < 0.01) between the two groups. There was a significant difference in RR of adverse events (AEs) of EVV (RR 1.49; 95% CI 1.27-1.74; I2 = 88%; P < 0.01), although no difference in RR of serious AE (SAE) between the two groups. Subgroup analysis showed that there was no significant difference in RR of AEs for DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines, compared with controls. CONCLUSIONS: The DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines are likely to be safe and immunogenic, tending to support the vaccination against Ebola disease. These findings should provide much-needed evidence for public health policy makers to develop preventive measures based on disease prevalence features and socio-economic conditions.

Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression.

Objective. Dysregulation of epithelial-mesenchymal transition (EMT) in the airway epithelium is associated with airway remodeling and the progression of pulmonary fibrosis. Many treatments have been shown to inhibit airway remodeling and pulmonary fibrosis progression in asthma and chronic obstructive pulmonary disease (COPD) by regulating EMT and have few side effects. This review aimed to describe the development of airway remodeling through the EMT pathway, as well as the potential therapeutic targets in these pathways. Furthermore, this study aimed to review the current research on drugs to treat airway remodeling and their effects on the EMT pathway. Findings. The dysregulation of EMT was associated with airway remodeling in various respiratory diseases. The cytokines released during inflammation may induce EMT and subsequent airway remodeling. Various drugs, including herbal formulations, specific herbal compounds, cytokines, amino acid or protein inhibitors, microRNAs, and vitamins, may suppress airway remodeling by inhibiting EMT-related pathways.

Nanotheranostic Trojan Horse for visualization and photo-immunotherapy of multidrug-resistant bacterial infection.

Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient imaging diagnosis of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate bacteria, both extracellularly and intracellularly. Further combined with photothermal therapy-induced immunogenic cell death and MP-MENP-mediated macrophage reprogramming, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrates dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promises a new way for complete eradication of MDR bacterial infection.

Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis.

BACKGROUND: Escitalopram is selective serotonin reuptake inhibitors (SSRIs) and one of the most commonly prescribed newer antidepressants (ADs) worldwide. We aimed to explore the efficacy, acceptability and tolerability of escitalopram in comparison with other ADs in the acute-phase treatment of major depressive disorder (MDD). METHODS: Medline/PubMed, EMBASE, the Cochrane Library, CINAHL, and Clinical Trials.gov were searched from inception to July 10, 2023. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. All randomized controlled trials comparing escitalopram against any other antidepressant for patients with MDD. Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, risk ratios (RRs) were calculated with 95% confidence intervals (CI). Continuous data were analyzed using standardized mean differences (with 95% CI) using the random effects model. RESULTS: A total of 30 studies were included in this meta­analysis, among which sixteen trials compared escitalopram with another SSRI and 14 compared escitalopram with a newer AD. Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (RR 0.67, 95% CI 0.50-0.87). Escitalopram was also more effective than citalopram in terms of remission (RR 0.53, 95% CI 0.30-0.93). CONCLUSIONS: Escitalopram was superior to other ADs for the acute phase treatment of MDD in terms of efficacy, acceptability and tolerability. However, no significant difference was found between escitalopram and other ADs in early response or follow-up response to treatment of MDD.

Radix Salvia miltiorrhiza Ameliorates Burn Injuries by Reducing Inflammation and Promoting Wound Healing.

Purpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats. Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue. Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-ß, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-ß1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney. Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.

Cascade signal amplification electrochemical biosensor based on AgNPs and ring opening polymerization for determination of Ochratoxin A.

An ochratoxin A (OTA) electrochemical biosensor based on a cascade signal amplification strategy with Ag nanoparticles (AgNPs) and ring opening polymerization (ROP) was constructed. The large specific surface area of AgNPs was used to increase the loading of OTA aptamer on the electrode surface, enhancing the ability to capture OTA as a way to achieve the first signal amplification. The OTA antibody modified with polyethylenimine specifically recognizes the OTA, forming an aptamer-OTA-antibody sandwich structure. The amino group on polyethylenimine initiates the ROP reaction with α-amino acid-n-carboxylic anhydride-ferrocene (NCA-Fc) as the monomer. A large number of electrochemical signal units of ferrocene are introduced into the sensing system for a second signal amplification. By amplifying the signal twice, the sensitivity of the sensor is improved. Under the optimal conditions, the detection range of the sensor is 1 pg·mL-1 ~ 1 µg·mL-1, while the detection limit is as low as 117 fg·mL-1. Moreover, the sensor has the advantages of high sensitivity, good stability and selectivity. Standard addition recovery experiment proved that the sensing system can be successfully used for the detection of OTA in four actual samples with recoveries in the range 90.0 to 113% with RSDs of 0.6 to 5.2%, providing a new idea for the pollution assessment of mycotoxins.

Nitrogen-Doped Graphene Quantum Dots as Electrochemiluminescence-Emitting Species for Sensitive Detection of KRAS G12C Mutation via PET-RAFT.

The levels of KRAS G12C point mutation is recognized to be closely related to the earlier diagnosis of non-small cell lung cancer (NSCLC). Here, based on nitrogen-doped graphene quantum dots (NGQDs) and photo-induced electron/energy transfer reversible addition-fragment chain transfer (PET-RAFT) signal amplification strategy, we fabricated a novel electrochemiluminescence (ECL) biosensor for the detection of KRAS G12C mutation for the first time. NGQDs as ECL-emitting species with cathodic ECL were prepared by a simple calcination method. Firstly, KRAS G12C mutation DNA, i. e., target DNA (tDNA), was captured by specific identification with hairpin DNA (hDNA). Then, PET-RAFT was initiated by blue light, and large numbers of monomers were successfully polymerized to form controllable polymer chains. Lastly, massive NGQDs was introduced via amidation reaction with N-(3-aminopropyl)methacrylamide hydrochloride (APMA), which significantly amplified the ECL signal intensity. Under optimal conditions, this biosensor achieved a good linear relationship between ECL intensity and logarithm of the levels of KRAS G12C mutation in the range from 10 fM to 10 nM. Moreover, this strategy exhibited high selectivity and excellent applicability for KRAS G12C mutation detection in the serum samples. Therefore, this biosensor has great potential in clinical diagnosis and practical application.

Mulberry fruit repairs alcoholic liver injury by modulating lipid metabolism and the expression of miR-155 and PPARα in rats.

As alcohol consumption increases, alcoholic liver disease (ALD) has become more popular and is threating our human life. In this study, we found mulberry fruit extract (MFE) repaired alcohol-caused liver diseases by regulating hepatic lipid biosynthesis pathway and oxidative singling in alcoholically liver injured (ALI) rats. MFE administration inhibited hepatic lipid accumulation and improved liver steatosis in ALI rats. MFE also enhanced the antioxidant capacity and alleviated the inflammatory response by increasing the activities of antioxidant enzymes and decreasing the contents of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Additionally, MFE regulated the expression of miRNA-155 and lipid metabolism-related PPARα protein in rats. Both miR-155 and PPARα play important roles in liver function. The results indicate that MFE has hepatoprotective effects against ALI in rats.

Lycopene alleviates food allergy by modulating the PI3K/AKT pathway in peanut-sensitized BALB/c mice.

Food allergies, which lead to life-threatening acute symptoms, are considered an important public health problem. Therefore, it is essential to develop efficient preventive and treatment measures. We developed a crude peanut protein extract (PPE)-induced allergy mouse model to investigate the effects of lycopene on peanut allergy. Mice were divided into four groups: 5 mg/kg lycopene, 20 mg/kg lycopene, no treatment, and control groups. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. In addition, pathology and immunohistochemistry analyses were used to examine the small intestine of mice. We found that lycopene decreased PPE-specific immunoglobulin E (IgE) and IL-13 levels in the serum, relieved small intestine inflammation, attenuated the production of histamine and mouse mast cell protease-1, and downregulated PI3K and AKT1 expression in the small intestine tissues of mice allergic to peanuts. Our results suggest that lycopene can ameliorate allergy by attenuating the PI3K/AKT pathway and the anaphylactic reactions mediated by PPE-specific IgE.

Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature.

Background: Gut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. Objective: We sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. Methods: Peanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE+B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. Results: BNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE+ B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. Conclusions: BNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.