Potential Effects Research Articles

Research of active compounds from Allii Macrostemonis Bulbus and potential targets against Non-Hodgkin's Lymphoma based on Network pharmacology.

Non-Hodgkin's Lymphoma (NHL) is a series of lymphoid malignancies in some aggressive subtypes with unsatisfactory treatment effects. Allii Macrostemonis Bulbus (Xie Bai) is a traditional Chinese medicine with anti-cancer activities, which may potentially suppress aggressive NHL. This study tries to discover active components and targets of Xie Bai in treating NHL by network pharmacology-based approaches. Compounds and related targets of Xie Bai were collected from the Traditional Chinese Medicine Database and Analysis Platform. Target genes associated with NHL were searched by GeneCards and DisGeNET, then the overlapped targets were further analyzed by STRING tool, GO, and KEGG pathway enrichment analysis. Molecular docking was employed to verify the interaction between compounds and targets. 11 bioactive compounds were successfully identified, with 30 targets that were screened out for the treatment of NHL. Functional enrichment analysis suggested that Xie Bai exerted its potential effects against NHL via pathways in cancer, such as PI3K/ AKT, p53, and MAPK signaling pathways. Molecular docking results showed that 3 active compounds (quercetin, beta-sitosterol, and naringenin) had good affinity with selected 6 targets（TP53, AKT1, CASP3, CCND1, HPK1, and NLRP3). Identifying six potential genes could accurately be docked with Xie Bai and had close interactions with NHL, which may provide insight into further research and new treatment strategy.

Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin.

The aim of this study was the preparation of mesoporous silica nanoparticles co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation of HN5 cells exposed to Rut-Cur-MSNs was evaluated. Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals; however, their low aqueous solubility and poor bioavailability limited their applications. The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the objective of this study. The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut-Cur-MSNs was assessed compared to control untreated cells. The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05). The achieved results recommend that the prepared mesoporous silica nanoparticles containing rutin and curcumin can be a useful nanoformulation for the treatment of cancer. The produced nanomaterial in this study can be helpful for cancer therapy.

Combining Cisplatin with Pinellia pedatisecta Schott Lipid-Soluble Extract Induces Tumor Immunogenic Cell Death in Cervical Cancer

BackgroundPinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PurposeTo explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. MethodsCervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. ResultsPE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. ConclusionsThis study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Targeting BTLA with the peptide inhibitor HVEM(14-39) – A new way to restore the activity of T cells in melanoma

The complex of B- and T-lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) plays a critical role in immune regulation and has emerged as a promising therapeutic target for cancer treatment. In this study, we investigated the potential of the peptide inhibitor HVEM(14-39) to restore peripheral T cell activity in patients with advanced melanoma. In these patients, CD8+ T cells downregulated BTLA expression and increased HVEM expression upon activation. The addition of HVEM(14-39) reduced the percentage of BTLA+ CD8+ T cells and increased the subpopulation of HVEM+ CD8+ T cells. Additionally, HVEM(14-39) enhanced T cell activation, proliferation, and the shift toward effector memory T cell subpopulations. Finally, this peptide affected the proliferation rate and late apoptosis of melanoma cell line in co-culture with T cells. These findings suggest that HVEM(14-39) can overcome T cell exhaustion and improve antitumor responses. Peptide-based immunotherapy targeting the BTLA-HVEM complex offers a promising alternative to monoclonal antibody-based therapies, with the potential for fewer side effects and higher treatment efficacy.

Acupuncture for the Treatment of Diabetes Related Distal Sensory Neuropathy: A Review of Study Designs and Quality of Randomized Controlled Trials

Diabetes affects nearly every organ system in the body, including the peripheral nervous system, and leads to the development of distal sensory peripheral neuropathy (DSP) in roughly 50% of patients. Between 30% to 50% of patients with DSP experience pain and impaired quality of life. Dissatisfaction with currently available pharmacological treatments for neuropathic pain is common, primarily due to limited effectiveness and potential for adverse side effects. Acupuncture, a non-pharmacologic intervention, is often used in the management of chronic pain and is widely available and acceptable to many patients. In this narrative review, we describe clinical research related to acupuncture and diabetes related DSP management including meta-analyses, systematic reviews, and randomized controlled clinical trials (RCTs). Data from the few clinical trials available support the use of acupuncture to reduce neuropathic pain including DSP pain; however, available studies suffer from methodological weaknesses including inadequate blinding, sample size justification, lack of well-designed controls, and gaps in reporting. These limitations highlight a critical gap and an unmet need for more rigorous and robust clinical research requiring the use of Standards for Reporting Clinical Trials of Acupuncture (STRICTA) guidelines as a design, implementation, and reporting template.

The influence of a course of complex application of supravenous laser irradiation of blood and phototherapy on indicators of the neurohormonal status of patients with true eczema

BACKGROUND: In the pathogenesis of true eczema, an important place is occupied by stress, under the influence of which stimulation of the hypothalamus and brain stem occurs, as well as activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. Stress-induced secretion of neurotransmitters impairs the barrier function of the epidermis, slows wound healing, increases itching and inflammation, and suppresses immunity by changing the immune response of T-helper cells. AIM: Assessment of the severity of the corrective effect of a course of application of supravenous laser irradiation of blood and broadband medium-wave phototherapy on the blood levels of adrenocorticotropin, cortisol and beta-endorphin in patients with true eczema with a moderate form of the course. MATERIALS AND METHODS: The study was carried out with the participation of 120 patients with a moderate form of true eczema. Using simple fixed randomization, all patients were divided into 4 groups. The first group (control, n=30) received only basic drug therapy, including the use of detoxification, hyposensitizing, antihistamines and topical glucocorticosteroids. Patients of the second group (comparison group 1, n=30) additionally underwent a course of supravenous laser irradiation of blood. In the third group (comparison group 2, n=30), broadband medium-wave phototherapy was performed against the background of basic therapy. Patients of the fourth group (main group, n=30) in addition to basic therapy received a course of combined exposure to supravenous laser blood irradiation and phototherapy. The concentrations of adrenocorticotropin, cortisol and beta-endorphin were determined in the blood of patients twice (before the start of treatment and 1 month after the start of therapy) using ELISA. The clinical condition of patients in the groups was assessed by changes in the EASI index. Additionally, we studied the dynamics of the level of reactive and personal anxiety using the Spielberger–Khanin questionnaire. RESULTS: Positive dynamics of adrenocorticotropin, cortisol and beta-endorphin were noted only in the comparison groups and the main group, which proves the high efficiency of correction of the neurohumoral status of patients through a course of complex use of supravenous laser blood irradiation and broadband mid-wave phototherapy. Quantitative changes in the assessed parameters during complex therapy with therapeutic physical factors indicate a supra-additive version of their interaction, realized through different modalities, points of application and mechanisms for realizing the biological potential of physiotherapeutic effects. CONCLUSION: The results obtained convincingly prove the effectiveness of an additional course of use of supravenous laser irradiation of blood in combination with broadband medium-wave phototherapy when correcting the neuroendocrine status in patients with true eczema. The close correlation between neurohumoral indicators and clinical and psychological patterns of the disease proves the pathogenetic significance of the studied neuroendocrine indicators, which allows us to consider their dynamics as informative criteria for the effectiveness of the treatment.

Sonic sensations: Navigating the mixed outcomes of ASMR in retail advertising

This paper investigates the influence of Autonomous Sensory Meridian Response (ASMR) elements in advertising on consumer attitudes. Through three experimental studies, we assess the impact of ASMR on attitudes toward ads and brands across hedonic and utilitarian product categories, and for known and unknown brands. Our findings reveal a generally negative effect of ASMR on ad attitudes among the wider population but identify a positive impact among those who experience ASMR's physiological sensations, as serially mediated through physiological and emotional responses. Notably, negative brand attitudes were observed only with unknown brands. This research underscores the nuanced role of ASMR in advertising, highlighting the potential for positive effects within a specific consumer segment, while cautioning against its broader application.

Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

Assessment of health risks from potassium bromate and trace metals in bread consumption in Ado Ekiti, Southwest, Nigeria

IntroductionBread, a staple food consumed by a large portion of the population worldwide, including Nigeria, has emerged as one of the most popular quick meal options. The excessive intake of potassium bromate and trace metals in bread has been identified as detrimental to human health due to its heightened propensity to induce cancer in human. ObjectiveThe current study assessed the exposure to potassium bromate (KBrO3) and trace metals through bread consumption, as well as the associated risks to dietary habits among Ado Ekiti, Southwest Nigeria residents. Bread varieties commonly consumed in Ado Ekiti were randomly chosen from local bakeries. These bread samples were then analyzed in the laboratory using an Atomic Absorption Spectrophotometer to determine the levels of trace metals, including lead (Pb), manganese (Mn), nickel (Ni), chromium (Cr), zinc (Zn), cadmium (Cd), and cobalt (Co), as well as potassium bromate concentrations. ResultsThe findings revealed that cobalt (Co) had the highest mean concentration (29.35±3.59 mg.kg−1), whereas lead (Pb) exhibited the lowest mean concentration (0.06±0.02 mg.kg−1). The sequence of trace metal levels was Co > Cd > Zn > Ni > Mn > Cr > Pb. All trace metal concentrations exceeded the standards set by FAO/WHO. Regarding potassium bromate content, it ranged from 0.01 mg.kg−1 to 0.06 mg.kg−1, surpassing the maximum permissible limits of 0.02 mg.kg−1 set by the Food and Drug Administration.Although the chronic hazard quotient among adults and children was low, the hazard ratio ranged from 11 to 9 among adults and from 14 to 9 among children, suggesting the potential for carcinogenic effects with repeated consumption. Based on the hazard ratios, the estimated chances of developing cancer from daily consumption of bread samples were approximately 14 in 1,000,000, 86 in 1,000,000, 71 in 1,000,000, and 40 in 1,000,000, respectively, for the adult population, and about 20 in 1,000,000, 11 in 1,000,000, 90 in 1,000,000, and 56 in 1,000,000 for the children population. ConclusionThe study showed that trace metals Pb, Mn, Ni, Cr, Zn, Cd and Co concentrations were higher than the FAO/WHO permissible limits. The concentration of potassium bromate in all the sorted bread samples exceeded the maximum acceptable limits except one. Though chronic hazard quotient among adults and children was low, the hazard ratio among the adult and children population was high, signifying possible cancer risks when continually consumed. These findings underscore the importance of stringent oversight by Nigerian regulatory authorities over using potassium bromate as an ingredient in bakeries.

Tumor-Tailored Ionizable Lipid Nanoparticles Facilitate IL-12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy.

The advancement of message RNA (mRNA) -based immunotherapies for cancer is highly dependent on the effective delivery of RNA (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, a high-throughput combinatorial method is utilized to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors. The lead LNP, H1L1A1B3, demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315, the industry-standard LNPs, while providing potent immune activation. A single intratumoral injection of H1L1A1B3 LNPs, loaded with circRNA encoding interleukin-12 (IL-12), induces a robust immune response in a Lewis lung carcinoma model, leading to marked tumor regression. Immunological profiling of treated tumors reveals substantial increments in CD45+ leukocytes and enhances infiltration of CD8+ T cells, underscoring the ability of H1L1A1B3 LNPs to modulate the tumor microenvironment favorably. These results highlight the potential of tailored LNP platforms to advance RNA drug delivery for cancer therapy, broadening the prospects for RNA immunotherapeutics.

A non-microcystin-producing Microcystis wesenbergii strain alters fish food intake by disturbing neuro-endocrine appetite regulation

Cyanobacterial harmful algal blooms (cHABs) are pervasive sources of stress resulting in neurotoxicity in fish. A member of the widely distributed Microcystis genus of bloom-forming cyanobacteria, Microcystis wesenbergii can be found in many freshwater lakes, including Dianchi Lake (China), where it has become one of the dominant contributors to the lake's recurrent blooms. However, unlike its more well-known counterpart M. aeruginosa, the effects of dense non-microcystin-containing M. wesenbergii blooms are seldom studied. The disturbance of appetite regulation and feeding behaviour can have downstream effects on the growth of teleost fish, posing a significant challenge to aquaculture and conservation efforts. Here we examined the effects of M. wesenbergii blooms on the food intake of Acrossocheilus yunnanensis, a native cyprinid in southern China. This fish species has disappeared in Dianchi Lake, and its reintroduction might be negatively affected by the presence of this newly-dominant Microcystis species. We co-cultured juvenile A. yunnanensis with a non-microcystin-producing strain of M. wesenbergii at initial densities between 5 × 104 and 1 × 106 cells/mL and monitored fish feeding behaviour and changes in neurotransmitter and hormone protein levels. High-density M. wesenbergii cultures increased the feeding rate of co-cultured fish, elevating concentrations of appetite-stimulating signalling molecules (Agouti-related protein and γ-aminobutyric acid), while decreasing inhibitory ones (POMC). These changes coincided with histopathological alterations and reduced somatic indices in brain and intestinal tissues. Given this potential for detrimental effects and dysregulation of food intake, further studies are necessary to determine the impacts of chronic exposure of M. wesenbergii in wild fish.

Impact of Prolonged Sport Stoppage on Knee Injuries in High School Athletes: An Ecological Study.

In March 2020, public health concerns resulted in school closure throughout the United States. The prolonged sport cessation may affect knee injury risk in high school athletes. The purpose of this study was to describe and compare risk of knee injuries in high school athletes during 2019-2020 and 2020-2021 academic years, and stratify by gender, severity, mechanism of injury, injury type, and knee anatomic region. Historical-prospective cohort study. This historical-prospective cohort study included 176 schools in 6 states matched by sport participation in control and COVID years from July 1, 2019 to June 30, 2021. Injury rates per 1000 athletes per year were calculated with 95% confidence intervals. A negative binomial regression was performed to assess potential differences in knee injuries between academic years. 94,847 and 72,521 high school athletes participated in the 2019-2020 (19-20) and 2020-2021 (20-21) seasons. Knee injury risk was higher in the 20-21 season (19-20: 28.89% [27.82-29.96]; 20-21: 33.82% [32.50-35.14]). Risk increased for male athletes from 2019-2020 to 2020-2021 (19-20: 29.42% [28.01-30.83]; 20-21: 40.32% [38.89-41.75]). Female knee injury risk was similar between years (19-20: 25.78% [24.29-27.27]; 20-21: 26.03% [24.31-27.75]). Knee injuries increased by a ratio of 1.2 ([95% CI, 1.1-1.3], P < .001) during 2020-2021. Knee injury risk and relative risk increased among males in 2020-2021. Results indicate changes in knee injury risk following return from COVID shelter in place among high school athletes and implicate potential negative downstream effects of interrupted sports training and participation on high school injury risk.

Exploring the Dual Components and Mechanism of Panax notoginseng-Eucommia ulmoides for Managing Osteoporosis-Associated Lumbar Disc Herniation Using Network Pharmacology

Osteoporosis (OP) combined with lumbar intervertebral disc herniation (LDH) is a complex disease that exhibits limited efficacy in drug treatment, physical therapy, and surgical intervention, while also carrying potential side effects and risks. Traditional Chinese medicine treatment of OP combined with LDH primarily aims to address deficiencies and regulate the body. Several active ingredients found in Panax notoginseng and Eucommia ulmoides, such as quercetin and beta-sitosterol, have demonstrated the ability to enhance osteoblast proliferation and bone matrix synthesis. While historical literature contains mechanistic studies on individual herbs, there is a conspicuous dearth of comprehensive and systematic research on their mechanisms of action. By utilizing network pharmacology method, we identified 35 active ingredients present in Panax notoginseng and Eucommia ulmoides, along with 98 potential targets associated with the treatment of OP combined with LDH using Panax notoginseng-Eucommia ulmoides. Through protein-protein interaction network analysis, we identified 5 essential active ingredients (Quercetin, Beta-carotene, Kaempferol, Beta-sitosterol, and Notoginsenoside Fe) and 5 core targets (Nuclear factor kappa-B 3 [RELA], hypoxia-induciblefactor-1A [HIF-1A], Myelocytomatosis Viral Oncogene homolog [MYC], Transcription Factor AP-1 [JUN], and Estrogen Receptor 1 [ESR1]). The potential targets primarily involve IL-17, AGEs-RAGE, the TNF signaling pathway, and other pathways through which they exert therapeutic effects. The key active ingredient was docked with the core target molecule, resulting in all molecules exhibiting binding energies ≤-5 kcal/mol. This study provides preliminary evidence that treatment with Panax notoginseng-Eucommia ulmoides for OP combined with LDH may lead to improvements in inflammation, oxidative stress, cell proliferation, differentiation, and apoptosis, and cytokine regulation.

Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty Liver Disease in High Fat-diet Mice.

Traditional Chinese medicine (TCM) has the advantage of low toxicity of natural ingredients, multiple targets and effects, and low medication costs. It has unique advantages for metabolic and chronic diseases. Huangqin-Huanglian decoction (HQHLD) is composed of Scutellariae Radix, Coptidis Rhizoma, Rehmanniae Radix, and Gentianae Radix Et Rhozima; it has great potential for the treatment of NAFLD with the modern pharmacological research and TCM theory, but there is still a relative lack of research on the potential targets and pharmacological effects of HQHLD. In this work, we have used network pharmacology to predict the targets and signaling pathways of HQHLD, and validated NAFLD-related targets using the HFD model in order to explore more therapeutic drugs and methods for NAFLD. We collected the HQHLD ingredients and NAFLD targets through TCMSP, ETCM, DisGeNET, HGMD, MalaCards, OMIM, and TTD, built ingredients-target networks by Cytoscape, and screened key ingredients in HQHLD. DAVID and Metascape databases were used for GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking of the key ingredients and key targets was performed by AutoDock. We verified the effect of HQHLD on high-fat diet (HFD) mice by measuring the weight, liver weight index, and the level of TG, TC, LDL-C, and HDLC. HE staining and oil-red staining were performed to detect the damage and fat accumulation in the liver. The changes in INSR, PPAR-α, PPAR-γ, TNF-α, and caspase3 were experimented with WB. With the network pharmacology analysis, we found quercetin, baicalein, sitosterol, wogonin, oroxylin-A, glycyrrhizin, hydroberberine, berberine, sesamin, and carotene to be the main ingredients in HQHLD. According to KEGG pathway analysis, INSR, AKT, JNK1, PPAR-α, PPAR-γ, and the other 16 targets are the main targets of HQHLD in the treatment of NAFLD. We took HFD mice as the in vivo model of NAFLD. Our results showed that HQHLD could reduce liver weight, and TG and LDL-C levels, and increase HDL-C level in serum. By HE and oil red staining, we found that HQHLD could protect the morphology of hepatocytes and reduce fat in the liver. We also found HQHLD to protect the liver by increasing the expression of INSR and PPAR-α, and reducing the expression of PPAR-γ, TNF-α, and caspase3 in the liver. In conclusion, our study has firstly studied the main ingredients and key targets of HQHDL in treating NAFLD by network pharmacology analysis, and preliminarily confirmed that HQHLD could alleviate NAFLD in a multi-target way by lowering fatty acids, and decreasing insulin resistance, inflammation, and apoptosis in the liver.

Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.

The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.

A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-KB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

Subcutaneous administration of ceftazidime at 20 and 40 mg/kg produces theoretically therapeutic plasma concentrations for at least 120 hours in red-eared sliders (Trachemys scripta elegans).

To evaluate and compare the pharmacokinetic parameters of SC ceftazidime administered at 20 and 40 mg/kg to red-eared sliders. 8 adult red-eared sliders (Trachemys scripta elegans). In a sequential, 2-period study with a 3-week washout period between treatments, ceftazidime was administered SC to turtles at 20 and 40 mg/kg. Blood samples were collected from the subcarapacial sinus at 0, 24, 48, 72, 96, and 120 hours after ceftazidime administration. Plasma ceftazidime concentrations were quantified using reversed-phase HPLC. Mean plasma half-life after 20- and 40-mg/kg dosing was 39.75 ± 8.0 hours and 33.03 ± 6.56 hours, respectively. Mean maximum plasma concentration after 20- and 40-mg/kg dosing was 71.0 ± 15.93 µg/mL and 120.0 ± 30.62 µg/mL, respectively. Mean plasma ceftazidime concentrations remained ≥ 8 µg/mL, the theoretical MIC for various reptile pathogens for all time points. Results indicate that ceftazidime dosed at either 20 or 40 mg/kg produces plasma concentrations exceeding the theoretical MIC of various reptile pathogens for at least 120 hours. An ideal dosing interval could not be determined, as all plasma concentrations remained above the threshold of interest for all time points. Follow-up studies should focus on establishing a dosing interval and more rigorous monitoring for potential adverse effects.

Impact of temperature and humidity conditions as abiotic stressors on the phytochemical fingerprint of oat (Avena sativa L.) sprouts

This study aimed to evaluate the effect of temperature (20, 25, and 30 °C) and relative humidity (RH, 50, 55, and 60 %) as abiotic stressors during oat (Avena sativa L.) germination using a 2-level factorial design with central point. UPLC-QToF-MSE identified eighty polyphenols, nine avenanthramides, twelve lignans, and five phytosterols Notably, 100 % germination was achieved at 25 °C/60 % RH from day 3, yielding the longest radicle size. The highest content of most phenolic acids, avenanthramides, and lignans occurred at 30 °C/65 % RH, where 100 % germination was attained by day 5, but with a shorter radicle size. The best flavonoid and phytosterol profle was obtained at 20 °C/55 % RH, achieving only a 67 % germination rate. Therefore, while these conditions enhance the bioactive compound profile, the associate decrease in germination metrics suggests potential distress effects. Consideration of both photochemical outcomes and germination yield is crucial for comprehensive assessments in future applications.

N-acetylcysteine Attenuates Cigarette Smoke-induced Alveolar Epithelial Cell Apoptosis through Reactive Oxygen Species Depletion and Glutathione Replenish In vivo and In vitro.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. N-acetylcysteine (NAC) is well known for its antioxidant properties, along with potential protective effects on COPD. However, the molecular mechanism of NAC against the apoptosis of alveolar epithelial cells (AECs) in COPD remains unclear. This study aimed to explore the anti-apoptosis effect of NAC in COPD mice and alveolar epithelial cells. In the present study, the mouse model of COPD was established by cigarette smoke (CS), and mouse alveolar epithelial (MLE-12) cells were treated with cigarette smoke extract (CSE). TdT-mediated dUTP nick-end labeling (TUNEL) assay, reverse transcription polymerase chain reaction (RT-PCR), and western blot were performed to evaluate the effects of NAC on apoptosis, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Meanwhile, LButhionine- sulfoximine (BSO), a glutathione (GSH) inhibitor, was used to uncover the mechanism of COPD treatment by NAC. We found that NAC pretreatment could attenuate the protein levels of apoptosis, ER stress, and mitochondrial dysfunction-related genes caused by CS in vivo. Meanwhile, CSE could decrease MLE-12 cell viability, which was prevented by apoptosis inhibitor ZVAD-FMK but not necroptosis inhibitor necrostatin-1. Pretreatment of MLE-12 cells with NAC increased cellular GSH levels, inhibited cellular and mitochondrial reactive oxygen species (ROS) accumulation, and decreased protein level of apoptosis, ER stress, and mitochondrial dysfunctionrelated genes. Moreover, experiment results showed that BSO could completely reverse the beneficial effects of NAC. Our study confirmed that NAC can attenuate CS-induced AEC apoptosis via alleviating ROS-mediated ER stress and mitochondrial dysfunction pathway, and the mechanism was found to be related to replenishing the cellular GSH content.

Integrating emerging science to improve estimates of risk to wildlife from chemical exposure: What are the challenges?

Many jurisdictions require ecological risk assessments for terrestrial wildlife (i.e., terrestrial vertebrates) to assess potential adverse effects from exposure to anthropogenic chemicals. This occurs, for example, at contaminated sites and when new pesticides are proposed, and it occurs for chemicals that are in production and/or proposed for wide-scale use. However, guidance to evaluate such risks has not changed markedly in decades, despite the availability of new scientific tools to do so. In 2019, the Wildlife Toxicology World Interest Group of the Society of Environmental Toxicology and Chemistry (SETAC) initiated a virtual workshop that included a special session coincident with the annual SETAC North America meeting and which focused on the prospect of improving risk assessments for wildlife and improving their use in implementing chemical regulations. Work groups continued the work and investigated the utility of integrating emerging science and novel methods for improving problem formulation (WG1), exposure (WG2), toxicology (WG3), and risk characterization (WG4). Here we provide a summary of that workshop and the follow-up work, the regulations that drive risk assessment, and the key focus areas identified to advance the ability to predict risks of chemicals to wildlife. Integr Environ Assess Manag 2024;20:645-657. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).