Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats.

Cisplatin (CIS) is a platinum-derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti-inflammatory properties, in cisplatin-induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), IL-6 and IL-10 were measured to determine inflammatory activity. In addition, 8-OHdG and caspase-3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF-α, IL-1ß and IL-6 obtained in CIS-treated groups increased as well as IL-10 decreased, thereby elevating the inflammatory response. In addition, 8-OHdG and caspase-3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity-induced apoptosis. This study shows that tangeretin has beneficial effects on CIS-induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti-inflammatory properties of tangeretin.

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

Monitoring of Organochlorine Pesticides (OCP) in Hair Samples of Wild Herbivorous Mammals Living in Remote and Protected Areas of the Far East and Siberia of Russia.

Monitoring wildlife exposure to biological hazards is a critical component of the wildlife risk assessment. In this study 38 hair samples were collected from 8 different species from ten districts of Russian Far East and Siberia and analysed for the presence of organochlorine pesticides (OCP). 50% of the samples were contaminated with - p, p'-DDT, α-HCH and DDD. DDT was the main contaminant found in 13 sample at concentrations range of 14.3 to 369.5 pg/mg hair, mean 91.9 ± 89.7 pg/mg. α-HCH was detected in three samples with the concentrations range 29.9-180.2 pg/mg. The p, p'-DDD was found only in one hair sample of Siberian roe deer from Altai region at 52.6 pg/mg. The exposure level is depended on animals habitat location. The most contaminated region is Terney district which is in the proximity to the borders with China and North Korea where OCP are still in use.

The Impact of Three-Month Quercetin Intake on Quality of Life and Anxiety in Patients With Type II Diabetes Mellitus: An Early Data Analysis From a Randomized Controlled Trial.

BACKGROUND: Diabetes is a high-prevalence, major chronic metabolic disease demanding effective interventions. Quercetin, a phytochemical with potential health benefits, has garnered interest for its therapeutic properties. AIM: This study was designed to capture the early efficacy and clinical safety aspects following quercetin administration in patients with type II diabetes mellitus (T2DM). METHODS: The main study involved a randomized allocation procedure to assign non-insulin-treated patients attending the 4th Health Unit of Heraklion to intervention and control groups based on age and sex. The intervention group (n=50) received 500 mg of quercetin daily for 12 + (8 free intervals) + 12 weeks, alongside their usual treatment, while the control group (n=50) did not. After randomization, for the intermediary 12-week follow-up, data from 38 patients (intervention: 20; control: 18) were analyzed in this report. All subjects provided informed consent for the collection of anthropometric measurements, vital signs, daily habits data, and PiKo-6 spirometric readings. Additionally, participants responded to the Short Anxiety Screening Test (SAST) and the 36-Item Short Form Health Survey (SF-36) questionnaires. RESULTS: Thirty-eight participants were included (60% men and 40% women in the intervention group; 38.9% men and 61.1% women in the control group). In the treatment arm, Forced Expiratory Volume in the first second (FEV1) measured with PiKo-6 showed a Δ%- change for the intervention arm: +6.8%, control: -0.2% (p=0.059), systolic blood pressure; intervention: -7.4%, control: -3.7% (p=0.117), waist circumference; intervention: -1.5% control: -0.7% (p=0.455) and night-time sleep; intervention: +5.3%, control: +1.4% (p=0.926) were favourably influenced. The treatment group exhibited significant enhancements in both anxiety levels assessed by the anxiety symptoms scale (SAST-10, p=0.026) and quality of life evaluated by the SF-36 (p<0.001). CONCLUSIONS: Positive evidence is emerging for a pleiotropic effect of quercetin intake in patients with T2DM, specifically in terms of anxiety reduction and amelioration of life quality, in just 12 weeks of administration and without adverse effects, indicating clinical safety and underscoring its potential for integration in T2DM supportive care.

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy.

Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other's efficacy, paving the way for promising future therapeutic advancements.

Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Background: Diabetes is a rapidly growing global morbidity issue with high prevalence, and the associated dysglycemia leads to complications. Patients with type 2 diabetes mellitus (T2DM) often experience elevated anxiety levels, affecting their quality of life and diabetes management. This study investigated quercetin, a nutraceutical and potential senolytic with antioxidant activity, to detect its possible positive effect on the bio-clinical measurements and routine health of patients with T2DM. Methods: This prospective randomized controlled trial (RCT) investigated the clinical usefulness of quercetin in patients with T2DM receiving non-insulin medications. One hundred participants were stratified by age and sex (1:1) and randomized to control (n = 50) or intervention (n = 50) groups. The control received standard care only, while the intervention received 500 mg quercetin daily for 12 weeks, followed by an 8-week washout and a final consecutive 12-week supplementation period (total: 32 weeks), as adjunct to their usual care. Comprehensive health assessments, including blood analyses, were conducted at baseline and study termination. Quality of life and anxiety were assessed using the 36-item Short Form Health Survey (SF-36) and Short Anxiety Screening Test (SAST-10). Results: Eighty-eight patients with T2DM concluded the trial. Compared with the control, glycated hemoglobin (HbA1c) levels showed a significant decrease (Δ%-change: -4.0% vs. 0.1%, p = 0.011). Quercetin also significantly improved PiKo-6 readings (FEV1: 5.6% vs. -1.5%, p = 0.002), systolic blood pressure (-5.0% vs. -0.2%, p = 0.029), night-time sleep (11.6% vs. -7.3%, p < 0.001), anxiety levels (SAST-10) (-26.2% vs. 3.3%, p < 0.001), and quality of life (SF-36) (both physical and mental components, p < 0.001). Conclusions: Based on the current open-label study, quercetin appears to be a promising supplement for T2DM, providing lifestyle and care support. Further research is warranted to shift this potential from clinical usefulness and feasibility to multidisciplinary evidence.

Activity of zinc oxide and zinc borate nanoparticles against resistant bacteria in an experimental lung cancer model.

BACKGROUND: Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties. OBJECTIVES: This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines. METHODS: Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis. RESULTS: The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL. CONCLUSION: A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.

AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation.

The present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 µg/g AuNPs, 1.6 g/kg CS, and 10 µg/g CS-AuNPs were administered orally simultaneously with 10 mg/kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-α and IL-1ß levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.

Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Changes in Rat Mammary Tissue Architecture Following Pregnancy/Lactation Exposure to Glyphosate Alone or with 2,4-D and Dicamba.

The current study aimed to assess the possible endocrine disruptor effects on rat mammary tissue and reproductive organs during pregnancy and lactation when exposed to low doses of glyphosate and its combination with 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba. The study involved the exposure of pregnant Wistar rats to various regulatory-relevant doses of glyphosate, ranging from gestational day 6 until fine of the lactation period. Glyphosate doses corresponded to the European Union's glyphosate-acceptable daily intake (ADI; 0.5mg/kg bw/day) and no observed adverse effect level (NOAEL; 50mg/kg bw/day). The dose of the mixture of glyphosate, dicamba, and 2,4-D was at the European Union ADI for each herbicide namely 0.5, 0.002, and 0.3mg/kg bw/day, respectively. In the animals exposed to glyphosate NOAEL serum estradiol levels were increased compared to untreated animals, along with an upregulation of TNF-?, MMP-2, and MMP-9 as measured in mammary gland homogenates compared to non-treated animals. Moreover, in this group, a focally acute inflammatory infiltrate was observed in the mammary gland. Our study showed that short-term exposure to glyphosate at doses that are set as safe by regulators and thus without risk corroborated with a particular physiological state as gestation and lactation, can give rise to inflammatory changes in breast tissue in rats. These findings support the need for further evaluation of glyphosate and mixtures of glyphosate with other pesticides for public health protection, especially for those categories vulnerable to the potential endocrine disruptor properties of these pesticides such as pregnant women, newborns, and children.

Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study.

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-ß (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.

Role of vitamins beyond vitamin D3 in bone health and osteoporosis (Review).

The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and their potential roles in the development of osteoporosis. Epidemiological findings have demonstrated an association between vitamin deficiency and a higher risk of developing osteoporosis; vitamins are positively related to bone health upon their intake at the physiological range. Excessive vitamin intake can also adversely affect bone formation, as clearly demonstrated for vitamin A. Vitamins E (tocopherols and tocotrienols), K2 (menaquinones 4 and 7) and C have also been shown to promote osteoblast development through bone morphogenetic protein (BMP)/Smad and Wnt/ß­catenin signaling, as well as the TGFß/Smad pathway (α­tocopherol). Vitamin A metabolite (all­trans retinoic acid) exerts both inhibitory and stimulatory effects on BMP­ and Wnt/ß­catenin­mediated osteogenesis at the nanomolar and micromolar range, respectively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa­B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteoprotegerin (OPG), thus reducing the RANKL/OPG ratio and exerting anti­osteoclastogenic effects. Ascorbic acid can both promote and inhibit RANKL signaling, being essential for osteoclastogenesis. Vitamin K2 has also been shown to prevent vascular calcification by activating matrix Gla protein through its carboxylation. Therefore, the maintenance of a physiological intake of vitamins should be considered as a nutritional strategy for the prevention of osteoporosis.

Assessment of the effects of amphiphilic poly (N­vinylpyrrolidone) nanoparticles loaded with bortezomib on glioblastoma cell lines and zebrafish embryos.

Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (IC50 ~6.5 µg/ml) and in 3D multicellular tumor spheroids (IC50 ~8.5 µg/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.