Tumor-Targeted Squaraine Dye for Near-Infrared Fluorescence-Guided Photodynamic Therapy.

Many efforts have been made to develop near-infrared (NIR) fluorescent dyes with high efficiency for the NIR laser-induced phototherapy of cancer. However, the low tumor targetability and high nonspecific tissue uptake of NIR dyes in vivo limit their applications in preclinical cancer imaging and therapy. Among the various NIR dyes, squaraine (SQ) dyes are widely used due to their high molar extinction coefficient, intense fluorescence, and excellent photostability. Previously, benzoindole-derived SQ (BSQ) was prepared by incorporating carboxypentyl benzoindolium end groups into a classical SQ backbone, followed by conjugating with cyclic RGD peptides for tumor-targeted imaging. In this study, we demonstrate that the structure-inherent tumor-targeting BSQ not only shows a high fluorescence quantum yield in serum but also exhibits superior reactive oxygen species (ROS) generation capability under the 671 nm laser irradiation for effective photodynamic therapy (PDT) in vitro and in vivo. Without targeting ligands, the BSQ was preferentially accumulated in tumor tissue 24 h post-injection, which was the optimal timing of the laser irradiation to induce increments of ROS production. Therefore, this work provides a promising strategy for the development of photodynamic therapeutic SQ dyes for targeted cancer therapy.

Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.

Purpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb-antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant. Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype. Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan- 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang-1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san-1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang-1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups. Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.

Effects of Perilla frutescens Var. Acuta in Busulfan-Induced Spermatogenesis Dysfunction Mouse Model.

PURPOSE: The leaves of Perilla frutescens var. acuta (PFA) are generally reported to have antioxidant, anti-allergic, anti-inflammatory, and antitumor effects and commonly used as a traditional medicine in East Asia. This study aimed to investigate the protective effect and antioxidant activity of PFA on busulfan-induced testicular dysfunction, histological damage, oxidative stress (OS), sperm quality, and hormone levels using a mouse model. MATERIALS AND METHODS: C57BL/6 male mice were divided into four groups: control, busulfan-only treated, and varying concentrations of PFA (100 and 200 mg/kg) with busulfan. In the busulfan group, 40 mg/kg of busulfan was intraperitoneally injected to induce azoospermia. Mice were orally administered PFA for 35 consecutive days after busulfan administration. Samples were collected and assessed for testis/body weight, testicular histopathology, sperm quality, serum hormone levels, and OS to evaluate the effects of PFA treatment on spermatogenesis dysfunction induced by busulfan. RESULTS: The busulfan-induced testicular dysfunction model showed reduced testis weight, adverse histological changes, significantly decreased sex hormones and sperm quality, and attenuated OS. These results indicate that PFA treatment significantly increased testis weight, testis/body weight, epididymal sperm count, motility, and testosterone level compared with busulfan alone. PFA treatment also attenuated the busulfan-induced histological changes. Furthermore, compared with mice treated with busulfan alone, PFA supplementation upregulated the testicular mRNA expression of the antioxidant enzymes superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), with a decrease in malondialdehyde (MDA) production and an increase in SOD and GPx activities. CONCLUSIONS: This study shows that PFA exerts a protective effect against testicular damage by attenuating OS induced by busulfan. Our results suggest that PFA is a potentially relevant drug used to decrease the side effects induced by busulfan on testicular function and sperm during cancer chemotherapy.

Chemical Constituents of Halophyte Suaeda glauca and Their Therapeutic Potential for Hair Loss.

Suaeda glauca, a halophyte in the Amaranthaceae family, exhibits remarkable resilience to high salt and alkali stresses despite the absence of salt glands or vesicles in its leaves. While there is growing pharmacological interest in S. glauca, research on its secondary metabolites remains limited. In this study, chemical constituents of the aerial parts of S. glauca were identified using 1D- and 2D-NMR experiments, and its biological activity concerning hair loss was newly reported. Eight compounds, including alkaloids (1~3), flavonoids (4~6), and phenolics (7 and 8), were isolated. The compounds, except the flavonoids, were isolated for the first time from S. glauca. In the HPLC chromatogram, quercetin-3-O-ß-d-glucoside, kaempferol-3-O-ß-d-glucoside, and kaempferol were identified as major constituents in the extract of S. glauca. Additionally, the therapeutic potential of the extract of S. glauca and the isolated compounds 1~8 on the expressions of VEGF and IGF-1, as well as the regulation of Wnt/ß-catenin signaling, were evaluated in human follicle dermal papilla cells (HFDPCs) and human umbilical vein endothelial cells (HUVECs). Among the eight compounds, compound 4 was the most potent in terms of increasing the expression of VEGF and IGF-1 and the regulation of Wnt/ß-catenin. These findings suggest that S. glauca extract and its compounds are potential new candidates for preventing or treating hair loss.

Potential Antioxidant and Anti-Inflammatory Properties of Polyphenolic Compounds from Cirsium japonicum Extract.

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.

Antioxidant effects of phenolic compounds in through the distillation of Lonicera japonica & Chenpi extract and anti-inflammation on skin keratinocyte.

The phenolic compounds in Lonicera japonica & Chenpi distillation extract (LCDE) were thoroughly examined for their antioxidant and anti-inflammatory properties. Phenolic compounds in LCDE were analyzed for five peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS) and determined. Five phenolic compounds were identified from the samples and MS data. Ultrafiltration with LC analysis was used to investigate the ability of bioactive compounds to target DPPH. As a result, it was confirmed that the major compounds exhibited a high binding affinity to DPPH and could be regarded as antioxidant-active compounds. In addition, the anti-inflammatory effect of LCDE was confirmed in vitro, and signal inhibition of anti-inflammation cytokines, MAPK and NF-kB pathways was confirmed. Finally, Molecular docking analysis supplements the anti-inflammatory effect through the binding affinity of selected compounds and inflammatory factors. In conclusion, the phenolic compounds of the LCDE were identified and potential active compounds for antioxidant and anti-inflammatory activities were identified. Additionally, this study will be utilized to provide basic information for the application of LCDE in the pharmaceutical and pharmaceutical cosmetics industries along with information on efficient screening techniques for other medicinal plants.

Robot versus human barista: Comparison of volatile compounds and consumers' acceptance, sensory profile, and emotional response of brewed coffee.

The increasing trend of integrating robots into the food industry has sparked debates regarding their potential influence on consumer attitudes toward food technology. This study investigated volatile compound profiles via gas chromatography-mass spectrometry (GC-MS), consumer acceptability, sensory profiling, and emotional responses of consumers toward coffee samples brewed by robot and human baristas. Moreover, the effect of the robot experience on food technology neophobia (FTN) was investigated. The principal component analysis of the volatile compound profiles revealed that the samples by the robot barista exhibited a higher degree of similarity compared to those prepared by the human barista. The range of relative standard deviations of volatile compounds from the robot barista brewed coffee was 1.4-83.1% and the variation was smaller than that of the human barista, which was 5.0-118.3%. Participants had a significant decrease in FTN scores after evaluating the robot-brewed coffee (p < 0.05), but there was no significant difference in FTN scores before and after evaluating the coffee brewed by the human barista (p > 0.05). Sensory evaluation studies revealed no significant differences in acceptability ratings and purchase intentions between the two groups (p > 0.05). However, emotional responses to the coffee samples significantly varied, with the robot-brewed coffee inducing more dynamic and positive emotions and the human-brewed coffee inducing more static and positive emotions (p < 0.05). Overall, this study provides valuable insights into consumer attitudes toward food robot service to humans and indicates that consumer's experience with food robots may significantly reduce FTN (p < 0.001).

Development of a Concurrent Treatment Technique of Ethyl Formate and Mixtures (Nitrogen, Phosphine) to Control Citrus Mealybug (Planococcus citri).

Currently, the fumigant ethyl formate (EF) is stored as a liquified gas in metal cylinders mixed with carbon dioxide (CO2), but this product type is expensive to manufacture, transport, and maintain in cylinders. To address these problems, we developed a new EF fumigation technique with a nitrogen (N2) carrier. In this report, the susceptibility of citrus mealybugs, one of the most resistant mealybugs to fumigants, to EF was assessed; the phytotoxicity of an EF + N2 concurrent treatment applied to banana fruit was examined to evaluate the efficacy compared to the current EF + CO2 product; and the increased efficacy with a phosphine (PH3) addition to EF + N2 was also assessed. Concurrent treatment of EF and N2 was performed at an LC50 concentration of EF. N2 was applied in seven doses from concentrations of 79% to 95%. The phytotoxicity of EF to bananas was assessed by applying EF at 35 mg/L with N2 at 79%, and the color, sugar content, and weight loss of bananas were measured for 14 days after treatment. The EF with N2 treatment resulted in more than 50% mortality at all growth stages of the mealybug, and there was no significant difference between the untreated and treated banana fruits. EF mixed with PH3 showed a higher efficacy than treatment with EF alone, but only a slight increase in efficacy was observed when the PH3 concentration increased. These results indicate that concurrent treatment with EF and N2 can be used to control mealybugs on banana fruits, and combined treatment with EF and PH3 can also enhance the efficacy against mealybugs.

Production of S-methyl-methionine using engineered Saccharomyces cerevisiae sake K6.

S-methyl-methionine (SMM), also known as vitamin U, is an important food supplement produced by various plants. In this study, we attempted to produce it in an engineered microorganism, Saccharomyces cerevisiae, by introducing an MMT gene encoding a methionine S-methyltransferase from Arabidopsis thaliana. The S. cerevisiae sake K6 strain, which is a Generally Recognized as Safe (GRAS) strain, was chosen as the host because it produces a significant amount of S-adenosylmethionine (SAM), a precursor of SMM. To increase SMM production in the host, MHT1 and SAM4 genes encoding homocysteine S-methyltransferase were knocked out to prevent SMM degradation. Additionally, MMP1, which encodes S-methyl-methionine permease, was deleted to prevent SMM from being imported into the cell. Finally, ACS2 gene encoding acetyl-CoA synthase was overexpressed, and MLS1 gene encoding malate synthase was deleted to increase SAM availability. Using the engineered strain, 1.92 g/L of SMM was produced by fed-batch fermentation. ONE-SENTENCE SUMMARY: Introducing a plant-derived MMT gene encoding methionine S-methyltransferase into engineered Saccharomyces cerevisiae sake K6 allowed microbial production of S-methyl-methionine (SMM).

Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling.

Rice bran, a by-product of rice milling, is abundant in bioactive molecules and is highly recognized for its health-promoting properties, particularly in improving metabolic conditions. Building on this knowledge, we aimed to optimize the extraction conditions to maximize the functional efficacy of rice bran extract (RBE) and further validate its impact on lipid metabolism. We found that the optimized RBE (ORBE) significantly suppressed high-fat diet-induced weight gain, hyperlipidemia, and hepatosteatosis in mouse models. ORBE treatment not only suppressed lipid uptake in vivo, but also reduced lipid accumulation in HepG2 cells. Importantly, we discovered that ORBE administration resulted in activation of AMPK and inhibition of STAT3, which are both crucial players in lipid metabolism in the liver. Collectively, ORBE potentially offers promise as a dietary intervention strategy against hyperlipidemia and hepatosteatosis. This study underlines the value of optimized extraction conditions in enhancing the functional efficacy of rice bran.

Obesity mechanism after hypothalamic damage: Cohort analysis of neuroimaging, psychological, cognitive, and clinical phenotyping data.

Objective: The hypothalamus regulates energy homeostasis, and its damage results in severe obesity. We aimed to investigate the multifaceted characteristics of hypothalamic obesity. Methods: We performed multidimensional analyses of brain structure/function and psychological and behavioral phenotypes in 29 patients with hypothalamic damage (HD) (craniopharyngioma) and 31 controls (non-functional pituitary adenoma). Patients underwent structural and functional magnetic resonance imaging and completed self-reports and cognitive tasks. Results: Patients with HD showed significantly higher postoperative weight gain than controls. The HD group also showed significant hypothalamic damage and lower neural activation in the left caudate nucleus in response to food images. The HD group had significantly higher food inattention, lower satiety, and higher restrained eating behavior. Within the HD group, higher restrained eating behavior was significantly associated with lower activation in the bilateral fusiform gyrus. Conclusion: These results suggest that hypothalamic damage contributes to weight gain by altering the brain response, attention, satiety, and eating behaviors. The present study proposes novel neuro-psycho-behavioral mechanisms targeted for patients with hypothalamic obesity.

The Protective Role of Glutathione on Zinc-Induced Neuron Death after Brain Injuries.

Glutathione (GSH) is necessary for maintaining physiological antioxidant function, which is responsible for maintaining free radicals derived from reactive oxygen species at low levels and is associated with improved cognitive performance after brain injury. GSH is produced by the linkage of tripeptides that consist of glutamic acid, cysteine, and glycine. The adequate supplementation of GSH has neuroprotective effects in several brain injuries such as cerebral ischemia, hypoglycemia, and traumatic brain injury. Brain injuries produce an excess of reactive oxygen species through complex biochemical cascades, which exacerbates primary neuronal damage. GSH concentrations are known to be closely correlated with the activities of certain genes such as excitatory amino acid carrier 1 (EAAC1), glutamate transporter-associated protein 3-18 (Gtrap3-18), and zinc transporter 3 (ZnT3). Following brain-injury-induced oxidative stress, EAAC1 function is negatively impacted, which then reduces cysteine absorption and impairs neuronal GSH synthesis. In these circumstances, vesicular zinc is also released into the synaptic cleft and then translocated into postsynaptic neurons. The excessive influx of zinc inhibits glutathione reductase, which inhibits GSH's antioxidant functions in neurons, resulting in neuronal damage and ultimately in the impairment of cognitive function. Therefore, in this review, we explore the overall relationship between zinc and GSH in terms of oxidative stress and neuronal cell death. Furthermore, we seek to understand how the modulation of zinc can rescue brain-insult-induced neuronal death after ischemia, hypoglycemia, and traumatic brain injury.

Investigation of the factors responsible for the low oral bioavailability of alizarin using a sensitive LC-MS/MS method: In vitro, in situ, and in vivo evaluations.

Alizarin (1,2-dihydroxyanthraquinone) is an anthraquinone reddish dye widely used for painting and textile dyeing. As the biological activity of alizarin has recently attracted increasing attention from researchers, its therapeutic potential as complementary and alternative medicine is of interest. However, no systematic research has been conducted on the biopharmaceutical and pharmacokinetic aspects of alizarin. Therefore, this study aimed to comprehensively investigate the oral absorption and intestinal/hepatic metabolism of alizarin using a simple and sensitive tandem mass spectrometry method developed and validated in-house. The present method for the bioanalysis of alizarin has merits, including a simple pretreatment procedure, small sample volume, and adequate sensitivity. Alizarin exhibited pH-dependent moderate lipophilicity and low solubility with limited intestinal luminal stability. Based on the in vivo pharmacokinetic data, the hepatic extraction ratio of alizarin was estimated to be 0.165-0.264, classified as a low level of hepatic extraction. In an in situ loop study, considerable fractions (28.2%-56.4%) of the alizarin dose were significantly absorbed in gut segments from the duodenum to ileum, suggesting that alizarin may be classified as the Biopharmaceutical Classification System class II. An in vitro metabolism study using rat and human hepatic S9 fractions revealed that glucuronidation and sulfation, but not NADPH-mediated phase I reactions and methylation, are significantly involved in the hepatic metabolism of alizarin. Taken together, it can be estimated that the fractions of oral alizarin dose unabsorbed from the gut lumen and eliminated by the gut and liver before reaching the systemic circulation are 43.6%-76.7%, 0.474%-36.3%, and 3.77%-5.31% of the dose, respectively, resulting in a low oral bioavailability of 16.8%. Therefore, the oral bioavailability of alizarin depends primarily on its chemical degradation in the gut lumen and secondarily on first-pass metabolism.

Effects of Vitamin D Supplementation on Testosterone, Prostate, and Lower Urinary Tract Symptoms: A Prospective, Comparative Study.

PURPOSE: Several studies have associated the serum vitamin D level with total testosterone levels and the prostate volume. Herein, we investigated the effect of vitamin D supplementation on testosterone, prostate, and lower urinary tract symptoms (LUTS) in men. MATERIALS AND METHODS: Men over 40 years of age diagnosed with a vitamin D deficiency (25[OH]D <20 ng/mL) who received vitamin D supplementation for one year were included in the study and administered 25,000 IU of cholecalciferol every 2 weeks. Prostate ultrasound, uroflowmetry, postvoid residual urine volume measurement, and serological tests (serum testosterone levels, etc.) were performed upon diagnosis and one year later. Participants also answered the International Prostate Symptom Score (IPSS) and Aging Males' Symptoms Scale (AMS) questionnaires. RESULTS: A significant increase was observed in the vitamin D level following one year of vitamin D supplementation, with a significant decrease in the postvoid residual urine volume, total IPSS score and without a significant change in the prostate volume. Improved psychological subscale score of AMS questionnaire was observed with a statistical significance. CONCLUSIONS: Vitamin D supplementation suppressed the increase in the prostate volume and improved the LUTS. Although there is no direct effect on serum testosterone levels, vitamin D supplementation helped improve hypogonadal symptoms.

Efficacy of electroacupuncture in preventing nausea and vomiting after thyroidectomy: A prospective randomized controlled trial.

OBJECTIVE: Postoperative nausea and vomiting are regarded as a serious concern after thyroidectomy. Electroacupuncture shows the potential to reduce general anesthesia-related side effects. The aim of this study was to evaluate the efficacy of electroacupuncture in preventing postoperative nausea and vomiting that commonly occurs in patients after thyroidectomy. METHODS: This study was a prospective randomized controlled trial with a two-arm, patient blind structure. Sixty-four participants were randomly assigned to the acupuncture (n = 35) or control (n = 29) group. Patients in the acupuncture group received electroacupuncture and intradermal press needles. The primary endpoint was the incidence and severity of postoperative nausea and vomiting, and secondary endpoints were the length of hospital stay, pain severity, and postoperative in-hospital morbidity. RESULTS: The total incidence of postoperative nausea and vomiting was 40.6% (26/64). There was no difference in the incidence between the control (10/29, 34.5%) and acupuncture (16/35, 45.7%) groups (p = 0.362). The severity of postoperative nausea and vomiting was not different between the groups (p = 0.842). Length of hospitalization and postoperative complications were not different between the groups. CONCLUSION: In this randomized controlled trial, electroacupuncture treatment after thyroidectomy is safe and comparable to conventional anti-emetic therapy. TRIAL REGISTRATION: Clinical Research Information Service, KCT0001782. Registered on 26 January 2016.

Case-Control Study of Occupational Acute Myeloid Leukemia in the Republic of Korea.

Background: We conducted a case-control study to identify high-risk occupations and exposure to occupational hazards for acute myeloid leukemia (AML). Methods: When patients with AML admitted to the Department of Hematology in the study hospital for the first time are referred to the Department of Occupational and Environmental Medicine, data on occupation are collected by investigators to evaluate work-relatedness. Community-based controls were recruited through an online survey agency, and four controls per case were matched. Occupational information was estimated using structured questionnaires covering 27 specific occupations and 32 exposure agents. Conditional logistic regression analysis was performed by pairing cases and controls. Results: In the analysis of the risk of AML according to occupational classification, a significant association was found in paint manufacturing or painting work (OR = 2.22, 95% CI: 1.03-4.81) and aircrew (OR = 6.00, 95% CI: 1.00-35.91) in males, and in pesticide industry (OR = 6.89, 95% CI: 1.69-28.07) and cokes and steel industry (OR = 2.00, 95% CI: 1.18-22.06) in ≥60 years old. Moreover, the risk of AML increased significantly as the cumulative exposure to thinners increased. In the analyses stratified by sex and age, the association between pesticide exposure and AML was significant in males (OR = 3.28, 95% CI: 1.10-9.77) and in ≥60 years old (OR = 6.22, 95% CI: 1.48-26.08). Conclusion: This case-control study identified high-risk occupational groups in the Republic of Korea including paint manufacturers and painters, aircrew, and those who are occupationally exposed to pesticides or paint thinners.

Tumor Targeting with Methotrexate-Conjugated Zwitterionic Near-Infrared Fluorophore for Precise Photothermal Therapy.

Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy.

Effect of drug use in the treatment of acute ischemic stroke: A scoping review.

Background: Drugs of abuse have been associated with ischemic stroke; however, the clinical presentation, outcomes, and treatment data in this population are limited. The overall safety and efficacy of thrombolytic therapy and thrombectomy in these patients remain unclear. This scoping review summarizes published complications and clinical outcomes in patients with recent abuse of cocaine, methamphetamine (MA), cannabis, decongestant, opioids, alcohol, and 3,4-methylenedioxymethamphetamine (MDMA) presenting with acute ischemic stroke. Methods: We conducted a scoping review of the primary literature that assessed outcomes data of thrombolytic therapy or thrombectomy in drug users with acute ischemic stroke. We searched PubMed, Ovid Medline, and Web of Science. Demographic and stroke characteristics, treatment, complications, and clinical outcomes at last follow-up were collected and summarized. Results: We identified 51 studies in this review. Drugs of abuse of interest were cocaine (14 studies), MDMA (one study), MA (eight studies), cannabis (23 studies), alcohol (two studies), decongestants (one study), and opioids (two studies). Clinical presentation and stroke presentation were most commonly described features. Thrombectomy outcomes were reported for four patients total (two studies), all with history of cocaine use. Thrombolysis treatment and outcomes were reported for 8851 patients (five studies) with history of cocaine, alcohol, or cannabis. Both treatments were pursued in three patients (three studies). Treatment complications included intracerebral hemorrhage, vasospasm, and cerebral edema. Conclusion: Evidence for thrombolytic and thrombectomy treatment in drug users remains limited. Controlled studies are needed to examine complication profile and outcomes following thrombolytic and thrombectomy treatment in this population.

Administration of α-Klotho Does Not Rescue Renal Anemia in Mice.

Renal anemia is a common complication in chronic kidney disease (CKD), associated with decreased production of erythropoietin (EPO) due to loss of kidney function, and subsequent decreased red blood cell (RBC) production. However, many other factors play a critical role in the development of renal anemia, such as iron deficiency, inflammation, and elevated fibroblast growth factor 23 (FGF23) levels. We previously reported that inhibition of FGF23 signaling rescues anemia in mice with CKD. In the present study we sought to investigate whether α-Klotho deficiency present in CKD also contributes to the development of renal anemia. To address this, we administered α-Klotho to mice with CKD induced by an adenine-rich diet. Mice were sacrificed 24 h after α-Klotho injection, and blood and organs were collected immediately post-mortem. Our data show that α-Klotho administration had no beneficial effect in mice with CKD-associated anemia as it did not increase RBC numbers and hemoglobin levels, and it did not stimulate EPO secretion. Moreover, α-Klotho did not improve iron deficiency and inflammation in CKD as it had no effect on iron levels or inflammatory markers. Interestingly, Klotho supplementation significantly reduced the number of erythroid progenitors in the bone marrow and downregulated renal Epo and Hif2α mRNA in mice fed control diet resulting in reduced circulating EPO levels in these mice. In addition, Klotho significantly decreased intestinal absorption of iron in control mice leading to reduced serum iron and transferrin saturation levels. Our findings demonstrate that α-Klotho does not have a direct role in renal anemia and that FGF23 suppresses erythropoiesis in CKD via a Klotho-independent mechanism. However, in physiological conditions α-Klotho appears to have an inhibitory effect on erythropoiesis and iron regulation.

Structural and Functional Properties of Activator Protein-1 in Cancer and Inflammation.

The transcriptional machinery is composed of numerous factors that help to regulate gene expression in cells. The function and the fundamental role of transcription factors in different human diseases and cancer have been extensively researched. Activator protein-1 (AP-1) is an inducible transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and survival in cells. Dysfunctional AP-1 activity is seen in several diseases, especially cancer and inflammatory disorders. The AP-1 proteins are controlled by mitogen-activated protein kinases (MAPKs) and the NF-κB pathway. AP-1 inhibitors can be actively pursued as drug discovery targets in cancer therapy when used as a treatment to halt tumor progression. The consumption of phytochemicals in the diet is related to decreasing the incidence of cancer and proves to exhibit anticancer properties. Natural product targets AP-1 are effective cancer prevention and treatment options for various cancer types. Targeting AP-1 with natural products is an effective cancer treatment option for different cancer types. This review summarizes AP-1 subunit proteins, their structures, AP-1-related signaling, and its modulation by natural bioactive compounds.