Enhancing Photothermal/Photodynamic Therapy for Glioblastoma by Tumor Hypoxia Alleviation and Heat Shock Protein Inhibition Using IR820-Conjugated Reduced Graphene Oxide Quantum Dots.

We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO2/BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO2/CPP. As MnO2 can react with intracellular hydrogen peroxide to produce oxygen for alleviating the hypoxia condition in the acidic tumor microenvironment, the efficacy of PDT could be enhanced by generating more cytotoxic ROS with NIR light. Furthermore, quercetin (Q) was loaded to rGOQD through π-π interaction, which can be released in the endosomes and act as an inhibitor of heat shock protein 70 (HSP70). This sensitizes tumor cells to thermal stress and increases the efficacy of mild-temperature PTT with NIR irradiation. By simultaneously incorporating the HSP70 inhibitor (Q) and the in situ hypoxia alleviating agent (MnO2), the rGOQD/IR820/MnO2/Q/CPP can overcome the limitation of PTT/PDT and enhance the efficacy of targeted phototherapy in vitro. From in vivo study with an orthotopic brain tumor model, rGOQD/IR820/MnO2/Q/CPP administered through tail vein injection can cross the blood-brain barrier and accumulate in the intracranial tumor, after which NIR laser light irradiation can shrink the tumor and prolong the survival times of animals by simultaneously enhancing the efficacy of PTT/PDT to treat glioblastoma.

Near-Infrared Photoimmunotherapy Using a Protein Mimetic for EGFR-Positive Salivary Gland Cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on a monoclonal antibody (mAb) conjugated to a photosensitizer (IR700Dye). The conjugate can be activated by near-infrared light irradiation, causing necrotic cell death with high selectivity. In this study, we investigated NIR-PIT using a small protein mimetic (6-7 kDa, Affibody) which has more rapid clearance and better tissue penetration than mAbs for epidermal growth factor receptor (EGFR)-positive salivary gland cancer (SGC). The level of EGFR expression was examined in vitro using immunocytochemistry and Western blotting. Cell viability was analyzed using the alamarBlue assay. In vivo, the volume of EGFR-positive tumors treated with NIR-PIT using the EGFR Affibody-IR700Dye conjugate was followed for 43 days. It was found that NIR-PIT using the EGFR Affibody-IR700Dye conjugate induced the selective destruction of EGFR-positive SGC cells and restricted the progression of EGFR-positive tumors. We expect that NIR-PIT using the EGFR Affibody-IR700Dye conjugate can efficiently treat EGFR-positive SGC and preserve normal salivary function.

A study on incorporation of giloy (Tinosporacordifolia) for the development of shelf-stable goat milk based functional beverage.

Goat milk has achieved significant place in human diet owing to its enormous therapeutic properties. There exists a scope of value-addition of goat milk to potentiate its health benefits by incorporating herbs and plants. Giloy (Tinospora cordifolia), a traditional medicinal plant with rich bioactive composition, can enhance the bioactive properties and shelf-life of goat milk. To this end, a study was conducted to develop shelf-stable giloy-goat milk beverage (GGB) by adding debittered giloy juice to goat milk (GM) and analyse the detailed product profile including proximate composition, bioactive properties, sensory, rheological, and structural characterisation. GGB resulted in two-fold increase (P < 0.05) in antioxidant activity and total phenolic content, thus enhancing the bioactive properties of the beverage as compared to GM. Further, increase in the particle size of GGB was observed along with components interaction, which was confirmed by FTIR, scanning electron and fluorescent microscopy. Storage stability studies indicated that bioactive properties of GGB remained unaffected (P > 0.05) by the sterilization process up to 90 days and sensory characteristics were not compromised till 105 days of storage. Therefore, the developed GGB is considered to be a shelf-stable beverage that retains its bioactive and sensory properties even after sterilization, making it a promising functional dairy product.

Upcycling Romaine lettuce outer leaves by infrared blanching and hot air drying.

Romaine lettuce outer leaves, as opposed to the more commonly marketed heart, are typically discarded and present an opportunity for upcycling as dried powders. Duquesne Romaine lettuce was evaluated to quantify and compare quality attributes of fresh outer and heart leaves, dried powders following hot air drying, and dried powders following an infrared (IR) blanching pretreatment before drying. Attributes measured for fresh leaves included moisture, water activity (Aw), color, total soluble phenolics (TSP), and antioxidant capacity (AC). Drying kinetics and time/energy saving through IR blanching were evaluated. Attributes measured for dried powders included moisture, Aw, color, true density, water vapor isotherms, TSP, AC, cadmium (Cd) content, and pesticide residues. TSP, AC, Cd, and pesticide residues were higher, whereas moisture content and Aw were lower in fresh outer versus heart leaves. Hot air drying reduced TSP and AC to 63.6% and 35.2% of fresh values, respectively, whereas IR blanching further reduced TSP and AC to 37.3% and 25.4% in outer leave powders. On the other hand, TSP and AC increased 237% and 151%, respectively, for unblanched heart powders. Higher increase of TSP than AC in heart leaf powder may indicate synthesis of phenolic compounds activated by abiotic stresses such as cutting and high temperatures at the initial drying stage. IR blanching resulted in significant time/energy savings for drying of outer leaves. Microbial loads were substantially reduced during drying, although microbial population on outer leaves were more resistant. Safe to eat outer leaf Romaine lettuce powders can be produced, assuming appropriate agricultural practices.

Shuangshen ningxin formula attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial function.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen Ningxin Formula (SSNX) is a traditional Chinese medicine formula used to treat myocardial ischemia-reperfusion injury (MIRI). A randomized controlled trial previously showed that SSNX reduced cardiovascular events, and experiments have also verified that SSNX attenuated ischemia-reperfusion (I/R) injury. However, the mechanism of SSNX in the treatment of microvascular I/R injury is still unclear. AIM OF THE STUDY: To determine whether SSNX protects the microvasculature by regulating I/R induction in rats and whether this effect depends on the regulation of NR4A1/Mff/Drp1 pathway. METHODS: The anterior descending coronary artery was ligated to establish a rat MIRI model with 45 min of ischemia and 24 h of reperfusion. The rats were subjected to a 7-day pretreatment with SSNX and nicorandil, after which their cardiac function and microvascular functional morphology were evaluated through diverse methods, including hematoxylin and eosin (HE) staining, wheat germ agglutinin (WGA) staining, and transmission electron microscopy. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Additionally, serum levels of ET-1 and eNOS were determined through an enzyme-linked immunosorbent assay (ELISA). The expression levels of NR4A1, Mff, and proteins related to mitochondrial fission were examined by Western blot (WB). Cardiac microcirculation endothelial cells (CMECs) were cultured and the oxygen-glucose deprivation/reoxygenation (OGD/R) model was duplicated. Following treatment with SSNX and DIM-C-pPhOH, an NR4A1 inhibitor, cell viability was assessed. Fluorescence was used to evaluate mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening. Moreover, vascular endothelial function was evaluated through transendothelial electrical resistance (TEER), Transwell assays and tube formation assays. RESULTS: The results showed that SSNX reduced the infarction area and no-flow area, improved cardiac function, mitigated pathological alterations, increased endothelial nitric oxide synthase expression, protected endothelial function, and attenuated microvascular damage after I/R injury. I/R triggered mitochondrial fission and apoptotic signaling in CMECs, while SSNX restored mitochondrial fission to normal levels and inhibited mitochondrial apoptosis. A study using CMECs revealed that SSNX protected endothelial function after OGD/R, attenuating the increase in NR4A1/Mff/Drp1 protein and inactivating VDAC1, HK2, cytochrome c (cyt-c) and caspase-9. Research also shows that SSNX can affect CMEC cell migration and angiogenesis, reduce mitochondrial membrane potential damage, and inhibit membrane opening. Moreover, DIM-C-pPhOH, an NR4A1 inhibitor, partially imitated the effect of SSNX. CONCLUSION: SSNX has a protective effect on the cardiac microvasculature by inhibiting the NR4A1/Mff/Drp1 pathway both in vivo and in vitro.

Akt Signaling and Nitric Oxide Synthase as Possible Mediators of the Protective Effect of N-acetyl-L-cysteine in Prediabetes Induced by Sucrose.

The aim of this work was to evaluate possible mechanisms involved in the protective effect of N-acetyl-L-cysteine (NAC) on hepatic endocrine-metabolic, oxidative stress, and inflammatory changes in prediabetic rats. For that, normal male Wistar rats (60 days old) were fed for 21 days with 10% sucrose in their drinking water and 5 days of NAC administration (50 mg/kg, i.p.) and thereafter, we determined: serum glucose, insulin, transaminases, uric acid, and triglyceride levels; hepatic fructokinase and glucokinase activities, glycogen content, lipogenic gene expression; enzymatic and non-enzymatic oxidative stress, insulin signaling pathway, and inflammatory markers. Results showed that alterations evinced in sucrose-fed rats (hypertriglyceridemia, hyperinsulinemia, and high liver fructokinase activity together with increased liver lipogenic gene expression and oxidative stress and inflammatory markers) were prevented by NAC administration. P-endothelial nitric oxide synthase (P-eNOS)/eNOS and pAKT/AKT ratios, decreased by sucrose ingestion, were restored after NAC treatment. In conclusion, the results suggest that NAC administration improves glucose homeostasis, oxidative stress, and inflammation in prediabetic rats probably mediated by modulation of the AKT/NOS pathway. Administration of NAC may be an effective complementary strategy to alleviate or prevent oxidative stress and inflammatory responses observed in type 2 diabetes at early stages of its development (prediabetes).

Drawing your way out: Imagery rehearsal based art therapy (IR-AT) for post-traumatic nightmares in borderline personality disorder.

Posttraumatic nightmares (PTN) are a frequent symptom after a traumatic event and often play part in the psychopathology of patients with borderline personality disorder (BPD). Imagery rehearsal therapy (IRT) currently offers the best evidence for an effective treatment to reduce PTNs, although high drop-out rates are common. Art therapy in IRT may counteract this, by its indirect, nonverbal, and often playful approach that helps to break through avoidance. This case study focusses on the perception of a patient with BPD in an art therapy based IRT treatment for patients with PTNs. It tells the story of Aurelia, a 40-year-old woman who, within this treatment, processes traumatic contents of her childhood like physical and sexual violence, but also current interactional problems that manifest themselves in her nightmares. Following the IR-AT treatment for PTNs Aurelia noticed a reduction in her nightmares, was less afraid of them and felt calmer towards her trauma. She expressed herself in the art medium and by this developed more self-efficacy. Her process resulted in an integration of the trauma and a perceived decrease in borderline symptoms. Future research can build on this basis to further explore the mechanisms and effects of IR-AT for PTNs.

ATP-adenosine axis regulation combined with microneedle assisted photoimmunotherapy to boost the immunotherapy efficiency.

Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy.

Photoresponsive 'chemo-free' phytotherapy: formulation development for the treatment of triple-negative breast cancer.

Aim: The present investigation aimed to develop a chemo-free, nanophytosomal system to treat triple-negative breast cancer (TNBC) via a phyto-photo dual treatment strategy. Method: Size, shape, surface analysis, photoprovoked release profile, photothermal stability, (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay, apoptotic assay, DNA fragmentation, in vitro cellular uptake evaluation, mitochondrial membrane potential and caspase-3 assay, and photodynamic evaluation. Results: Biological experiments using MDA-MB-231 cells displayed dose-dependent synergistic anti-TNBC activity of PhytoS/Houttuynia cordata extract (HCE)/IR780 as compared with Phyto/HCE, PhytoS/IR780 and even more promising under laser treatment. Apoptotic assay and DNA fragmentation analysis also showed enhanced anti-TNBC effects. Investigation found that HCE acts via suppression of mitochondrial membrane potential and inducing caspase-3 activity in cells. Conclusion: Our findings suggested that photo-empowered phytotherapy can be employed effectively and safely against TNBC.

ResD-Net: A model for rapid prediction of antioxidant activity in gentian root using FT-IR spectroscopy.

Gentian, an herb resource known for its antioxidant properties, has garnered significant attention. However, existing methods are time-consuming and destructive for assessing the antioxidant activity in gentian root samples. In this study, we propose a method for swiftly predicting the antioxidant activity of gentian root using FT-IR spectroscopy combined with chemometrics. We employed machine learning and deep learning models to establish the relationship between FT-IR spectra and DPPH free radical scavenging activity. The results of model fitting reveal that the deep learning model outperforms the machine learning model. The model's performance was enhanced by incorporating the Double-Net and residual connection strategy. The enhanced model, named ResD-Net, excels in feature extraction and also avoids gradient vanishing. The ResD-Net model achieves an R2 of 0.933, an RMSE of 0.02, and an RPD of 3.856. These results support the accuracy and applicability of this method for rapidly predicting antioxidant activity in gentian root samples.

Identification and determination of different processed products and their extracts of Crataegi Fructus by infrared spectroscopy combined with two-dimensional correlation analysis.

The fruit of Crataegus sp. is known as "Shanzha (SZ)" in China and is widely used in the food, beverage, and traditional Chinese medicine (TCM) industries. SZ usually requires thermal processing to reduce the irritation of its acidity to the gastric mucosa. Different processed products of SZ resulting from thermal processing have different or even opposite functions in clinical applications. In addition, 5-hydroxymethylfurfural (5-HMF) intermediates produced during thermal processing are carcinogenic to humans. Therefore, the aim of this study was to explore a rapid and accurate method by Fourier transform infrared spectroscopy (FT-IR) for the identification of different processed products and the determination of 5-HMF in extracts. In qualitative identification, a three-stage infrared spectroscopy identification method (raw spectra, the second derivative spectra, and two-dimensional correlation (2DCOS) spectra) was developed to distinguish different processed products of SZ step by step. In quantitative determination, partial least squares regression combined with different variable selection methods, especially the 2DCOS method, was applied to determine the 5-HMF content. The results show that temperature-induced 2DCOS synchronous spectra can effectively identify different processed products of SZ by shape, intensity, and position of auto-peaks or cross-peaks, and the variables selected by power spectra from concentration-induced 2DCOS synchronous spectra have better prediction ability for 5-HMF compared to full variables. The above results demonstrate that 2D-COS analysis is a potential tool in qualitative and quantitative analysis, which can improve sample identification accuracy and determination capabilities. This study not only establishes a rapid and accurate method for the identification of different processed products but also provides a practical reference for food safety and the efficient use of TCM.

A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

Antioxidant isolation and characterization from the plant Tradescantia spathacea Sw. of the Commelinaceae family.

A novel bioactive flavan glycoside was isolated by solvent extraction method with the help of Soxhlet apparatus from the methanolic extract of Tradescantia spathacea Sw. Flavan glycoside having molecular formula C20H22O10, melting point 175-1780C, molecular weight by ESI-MS m/z (M + H]+ 423, optical rotation was[α]21D-45.1(c 0.20 methanol). Its structure was determined (-)-epicatechin 7-O-alpha-L-arabinopyranoside. Various color reactions, chemical degradation (like acid hydrolysis, permethylation, and enzymatic hydrolysis), UV-Visible spectrophotometry, Fourier transforms infrared spectroscopy, electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy were used to establish the structure of compound (-)-(-)-epicatechin 7-O-alpha-L-arabinopyranoside.. A flavan glycoside was also tested with a DPPH assay method for antioxidant activity by using Ascorbic acid as standard. DPPH radical scavenging test data demonstrate that a flavan glycoside possesses potent antioxidant activity so this flavan glycoside can be utilized as a potent antioxidant agent.

SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion.

SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.

Near-infrared photoimmunotherapy and anti-cancer immunity.

The activation of the anti-cancer immune system is an important strategy to control cancer. A new form of cancer phototherapy, near-infrared photoimmunotherapy (NIR-PIT), was approved for clinical use in 2020 and uses IRDye® 700DX (IR700)-conjugated antibodies and NIR light. After irradiation with NIR light, the antibody-IR700 conjugate forms water-insoluble aggregations on the plasma membrane of target cells. This aggregation causes lethal damage to the plasma membrane, and effectively leads to immunogenic cell death (ICD). Subsequently, ICD activates anti-cancer immune cells such as dendritic cells and cytotoxic T cells. Combination therapy with immune-checkpoint blockade has synergistically improved the anti-cancer effects of NIR-PIT. Additionally, NIR-PIT can eliminate immunosuppressive immune cells in light-irradiated tumors by using specific antibodies against regulatory T cells and myeloid-derived suppressor cells. In addition to cancer-cell-targeted NIR-PIT, such immune-cell-targeted NIR-PIT has shown promising results by activating the anti-cancer immune system. Furthermore, NIR-PIT can be used to manipulate the tumor microenvironment by eliminating only targeted cells in the tumor, and thus it also can be used to gain insight into immunity in basic research.

Salinomycin and IR780-loaded upconversion nanoparticles influence biological behavior of liver cancer stem cells by persistently activating the MAPK signaling pathway.

The combination of chemotherapy and phototherapy has emerged as a promising therapeutic approach for enhancing the efficacy of cancer treatment and mitigating drug resistance. Salinomycin (SAL), a polyether antibiotic, exhibits potent cytotoxicity against chemotherapy-resistant cancer cells. IR780 iodide, a novel photosensitive reagent with excellent near-infrared (NIR) light absorption and photothermal conversion abilities, is suitable for use in photothermal therapy for cancers. However, both SAL and IR780 exhibit hydrophobic properties that limit their clinical applicability. Upconversion nanoparticles (UCNPs) are an emerging class of fluorescent probe materials capable of emitting high-energy photons upon excitation by low-energy NIR light. The UCNPs not only function as nanocarriers for drug delivery but also serve as light transducers to activate photosensitizers for deep-tissue photodynamic therapy. Here, to enhance the targeting and bioavailability of hydrophobic drugs in liver cancer stem cells (LCSCs), we employ distearoyl phosphorethanolamine-polyethylene glycol (DSPE-PEG) to encapsulate SAL and IR780 on the surface of UCNPs. Cell viability was evaluated using the CCK-8 assay. Cell migration was assessed by the Transwell Boyden Chamber. The activation of the mitogen-activated protein kinase (MAPK) signaling pathway was measured via western blot. The results demonstrated successful loading of both IR780 and SAL onto the UCNPs, and the SAL and IR780-loaded UCNPs (UISP) exhibited a robust photothermal effect under NIR light irradiation. The UISP effectively inhibited the viability of HCCLM3 and LCSCs. Under NIR light irradiation, the UISP further suppressed HCCLM3 viability but had no impact on LCSC viability; however, it could further inhibit LCSC migration. Meanwhile, under NIR light irradiation, the UISP persistently activated the MAPK pathway more significantly in LCSCs. These findings suggest that exposure to NIR light results in persistent activation of the MAPK pathway by UISP, thereby influencing the biological behavior of LCSCs and enhancing their therapeutic efficacy against liver cancer.

Protective Effect of Compound Tongluo Decoction on Brain Vascular Endothelial Cells after Ischemia-Reperfusion by Inhibition of Ferroptosis Through Regulating Nrf2/ARE/SLC7A11 Signaling Pathway.

Cerebral infarction is one of the most common diseases for aged people. Compound Tongluo Decoction (CTLD), a classic traditional Chinese Medicine prescription, has been widely used in the treatment of ischemic cerebral infarction. Transient middle cerebral artery occlusion (tMCAO) rat model is established for the animal experiment and oxygen-glucose deprivation and reperfusion (OGD/R) human umbilical vein endothelial cells (HUVECs) model are established for the cell experiment. This also use Nrf2-/- rats to detect the role of nuclear factor erythroid 2-related factor 2 (Nrf2). Longa score, Evans blue staining, brain water content measurement, and histological observation are done. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and other ferroptosis-related components are detected respectively. In the vivo experiment, CTLD relieved ischemia-reperfusion (IR) injury symptoms and attenuated IR injury in brain tissues of tMCAO rats by relieving peroxidation injury in brain tissues and inhibiting ferroptosis in tMCAO rats. Moreover, CTLD reversed OGD/R-induced oxidative damage of endothelial cells via suppressing ferroptosis. After knocking out the Nrf2 gene, the protective effect of CTLD is sharply reduced. This study put forward that CTLD can inhibit ferroptosis in I/R-injured vascular endothelium by regulating Nrf2/ARE/SLC7A11 signaling to improve the relative symptoms of rats after cerebral I/R injury, thus providing a viable treatment option for cerebrovascular disease.

Exosomes with IR780 and Lenvatinib loaded on GPC3 single-chain scFv antibodies for targeted hyperthermia and chemotherapy in hepatocellular carcinoma therapy.

Exosomes (EXOs) are considered natural nanoparticles which have been widely used as carriers for the treatment and diagnosis of various diseases. However, due to the non-specific uptake, the unmodified EXOs cannot effectively deliver the vector to the target site. In this study, we used pDisplay vector to engineer Glypican-3 (GPC3) single-chain scFv antibody to the exosome surface, and the effect of engineered exosomes on the proliferation and migration of hepatocellular carcinoma (HCC) cells was determined by a series of in vitro experiments as well as in vivo mouse xenograft model and PDX model. Furthermore, we established an improved delivery system by engineering single-chain scFv antibody against GPC3 on the EXO surface for a more efficient HCC targeting. Moreover, the delivery system was loaded with IR780 and Lenvatinib for a combination of thermotherapy and chemotherapy. Our results revealed that the antibody-engineered exosomes enabled rapid imaging of HCC xenograft models post IR780 loading and showed significant anti-tumor photothermal therapy (PTT) effects after irradiation. Since dual loading of IR780 and Lenvatinib in exosomes required only a single injection and had a maximal efficacy against cancer cells, our findings highlight the clinical application of using GPC3 single-chain scFv antibody-engineered exosomes loaded with IR780 and Lenvartinib to achieve the imaging and the treatment of HCC from the combined effect of IR780-induced PTT and Lenvatinib-induced chemotherapy.

Phytochemical and Nutraceutical Screening of Ethanol and Ethyl Acetate Phases of Romanian Galium verum Herba (Rubiaceae).

Galium species are used worldwide for their antioxidant, antibacterial, antifungal, and antiparasitic properties. Although this plant has demonstrated its antitumor properties on various types of cancer, its biological activity on cutaneous melanoma has not been established so far. Therefore, the present study was designed to investigate the phytochemical profile of two extracts of G. verum L. herba (ethanolic and ethyl acetate) as well as the biological profile (antioxidant, antimicrobial, and antitumor effects) on human skin cancer. The extracts showed similar FT-IR phenolic profiles (high chlorogenic acid, isoquercitrin, quercitrin, and rutin), with high antioxidant capacity (EC50 of ethyl acetate phase (0.074 ± 0.01 mg/mL) > ethanol phase (0.136 ± 0.03 mg/mL)). Both extracts showed antimicrobial activity, especially against Gram-positive Streptococcus pyogenes and Staphylococcus aureus bacilli strains, the ethyl acetate phase being more active. Regarding the in vitro antitumor test, the results revealed a dose-dependent cytotoxic effect against A375 melanoma cell lines, more pronounced in the case of the ethyl acetate phase. In addition, the ethyl acetate phase stimulated the proliferation of human keratinocytes (HaCaT), while this effect was not evident in the case of the ethanolic phase at 24 h post-stimulation. Consequently, G. verum l. could be considered a promising phytocompound for the antitumor approach of cutaneous melanoma.

High dietary intake of unsaturated fatty acids is associated with improved insulin resistance - a cross-sectional study based on the NHANES database.

BACKGROUND: A moderate intake of unsaturated fatty acids (UFA) is associated positively with improved insulin resistance. The aim of this study was to investigate the relationship between the dietary intake of unsaturated fatty acids/total fats (UFA/TF) and insulin resistance. METHODS: 15,560 participants were selected from the National Health and Nutrition Examination Survey (NHANES) database enrolled between March 2017 and 2020, and excluded those under 20 years of age, pregnant, or with missing data for key research items. Finally, 7,630 participants were included in the study. R software was used for data analysis that included: (1) general descriptive statistics; (2) comparison of differences in baseline information of three UFA/TF groups, namely low, medium, and high ratios; (3) calculation of the correlation between the UFA/TF ratio and markers of insulin resistance: triglyceride-glucose index (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR); (4) stratification of the study subjects into two groups, with or without insulin resistance, using a cut-off value of HOMA-IR ≥ 2, followed by logistic regression analysis to examine the relationship between UFA/TF and insulin resistance status in the two groups; and (5) further stratification of the subjects according to age, gender, body mass index (BMI), race, total energy intake, total protein, total carbohydrate, total sugars, total dietary fiber, total fat, alcohol consumption, diabetes, hypercholesterolemia to analyze the impact of UFA/TF on insulin resistance status in different subgroups. RESULTS: (1) A high UFA/TF level was associated with a low TyG index and HOMA-IR [ß (vs. TyG index) = -0.559, 95% CI: (-0.821~-0.297), P < 0.001; ß (vs. HOMA-IR) = -0.742, 95% CI: (-1.083~-0.402), P < 0.001]. This negative relationship became more pronounced when UFA/TF exceeded 57.9% (i.e., the higher group). (2) Logistic regression analysis showed that a higher UFA/TF level was associated with a lower risk of developing insulin resistance [Q3 vs. Q1: 0.838 (95%CI: 0.709 ~ 0.991); P for trend = 0.038]. After adjusting for covariates such as gender, age, and BMI, this protective effect remained significant (P value < 0.05). (3) Analysis also showed that increased UFA/TF intake reduced the risk of developing insulin resistance (OR = 0.266, 95% CI: (0.075 ~ 0.946), P = 0.041). Subgroup analysis showed that although elevated UFA/TF intake showed no statistically significant difference in its effect in most subgroups, the large study population in this study provides valuable insights on potential changes. Increased UFA/TF intake may confer relatively greater benefits within specific subgroups, particularly among the elderly [Q3 age group, OR = 0.114, 95%CI: (0.012 ~ 1.078), P = 0.058], females [OR = 0.234, 95%CI: (0.041 ~ 1.333), P = 0.102], those with a BMI ≤ 25 kg/m²[OR = 0.191, 95%CI: (0.016 ~ 2.344), P = 0.196], and individuals without hypercholesterolemia [OR = 0.207, 95%CI: (0.042 ~ 1.013), P = 0.0519]. The impact of high UFA/TF levels within subgroups based on the presence or absence of coronary heart disease and stroke displayed contrasting trends. In those without coronary heart disease, there was a significant protective effect against insulin resistance [OR = 0.254, 95% CI: (0.07 ~ 0.929), P = 0.0384], while in the stroke subgroup, a significantly protective effect against insulin resistance was observed [OR = 0.002, 95%CI: (0 ~ 0.695), P = 0.0376]. CONCLUSION: A high dietary intake of UFA relative to total fat consumption could be a protective factor against the risk of developing insulin resistance.