Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a ...neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential.
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-Carnitine (LC) is regarded as the “gatekeeper” in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.
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Tauroursodeoxycholic acid (TUDCA) is approved for the treatment of liver diseases. However, the antihyperglycemic effects/mechanisms of TUDCA are still less clear. The present study aimed to evaluate ...the antidiabetic action of TUDCA in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) in rats. Fifteen adult Wistar albino male rats were randomly divided into three groups (n = five in each): control, diabetic (STZ), and STZ+TUDCA. The results showed that TUDCA treatment significantly reduced blood glucose, HbA1c%, and HOMA-IR as well as elevated the insulin levels in diabetic rats. TUDCA therapy increased the incretin GLP-1 concentrations, decreased serum ceramide synthase (CS), improved the serum lipid profile, and restored the glycogen content in the liver and skeletal muscles. Furthermore, serum inflammatory parameters (such as TNF-α, IL-6, IL-1ß, and PGE-2) were substantially reduced with TUDCA treatment. In the pancreas, STZ+TUDCA-treated rats underwent an obvious enhancement of enzymatic (CAT and SOD) and non-enzymatic (GSH) antioxidant defense systems and a marked decrease in markers of the lipid peroxidation rate (MDA) and nitrosative stress (NO) compared to STZ-alone. At the molecular level, TUDCA decreased the pancreatic mRNA levels of iNOS and apoptotic-related factors (p53 and caspase-3). In conclusion, TUDCA may be useful for diabetes management and could be able to counteract diabetic disorders via anti-hyperlipidemic, antioxidant, anti-inflammatory, and anti-apoptotic actions.
Accurate and reliable forecasts of malarial incidences are necessary for the health authorities to ensure the appropriate action for the control of the outbreak. In this study, a novel method based ...on coupling the Firefly Algorithm (FFA) and Support Vector Machines (SVM) has been proposed to forecast the malaria incidences. The performance of SVM models depends upon the appropriate choice of SVM parameters. In this study FFA has been employed for determining the parameters of SVM. The proposed SVM-FFA model has been adopted in predicting the malarial incidences in Jodhpur and Bikaner area where the malaria transmission is unstable. Monthly averages of rainfall, temperature, relative humidity and malarial incidences have been considered as input variables. Time series of monthly notifications of malaria cases has been obtained from primary health centers and from other local health facilities for a period of January 1998 to December 2002 in the region of Bikaner and from January 1998 to December 2000 in Jodhpur region. Further, the rainfall, relative humidity and temperature data have been obtained from meteorological records. The performance of the proposed SVM-FFA model has been compared with Artificial Neural Networks (ANN), Auto-Regressive Moving Average method and also with Support Vector Machine. The results indicate that the proposed SVM-FFA model provides more accurate forecasts compared to the other traditional techniques. Further, it has been recommended to carry out additional strides to explore the utility and efficacy of SVM-FFA model. Thus SVM-FFA can be an alternate tool to facilitate the control of vector borne diseases like malaria.
Metadherin (AEG-1/MTDH/LYRIC) is a 582-amino acid transmembrane protein, encoded by a gene located at chromosome 8q22, and distributed throughout the cytoplasm, peri-nuclear region, nucleus, and ...nucleolus as well as the endoplasmic reticulum (ER). It contains several structural and interacting domains through which it interacts with transcription factors such as nuclear factor-κB (NF-κB), promyelocytic leukemia zinc finger (PLZF), staphylococcal nuclease domain containing 1 (SND1) and lung homing domain (LHD). It is regulated by miRNAs and mediates its oncogenic function via activation of cell proliferation, survival, migration and metastasis, as well as, angiogenesis and chemoresistance via phosphatidylinositol-3-kinase/AKT (PI3K/AKT), NF-κB, mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. In this chapter, metadherin is reviewed highlighting its role in mediating growth, metastasis and chemoresistance in colorectal cancer (CRC). Metadherin, as well as its variants, and antibodies are associated with CRC progression, poorer prognosis, decreased survival and advanced clinico-pathology. The potential of AEG-1/MTDH/LYRIC as a diagnostic and prognostic marker as well as a therapeutic target in CRC is explored.
In the light of the COVID-19 pandemic, anti-vaccine sentiments have been on the rise, with a recent seminal study on the development of anti-vaccine views in social media even making its way into
...Nature Communications
. Yet, with the current scientific consensus being in overwhelming agreement over the safety and efficacy of vaccines, many scientists lose their grasp on the fears, concerns, and arguments that the opposition may hold. This paper discusses and evaluates vaccine-hesitant individuals on a socioeconomic, historical, and philosophical landscape. It also provides an analysis of common argumentative patterns and the psychological impact that these arguments may have on undecided individuals. The discussion also explores why anti-vaccine sentiments are on the rise, and how members of the scientific and medical community require a more structured approach to communicating key arguments. This is particularly important if vaccination rates and herd immunity are to be sustained. No longer is it sufficient to win arguments based on a factual and scientific basis, but rather scientists and medical practitioners have to focus on conveying confidence and reassurance on both an informative and emotional level to those with doubts and fears.
Air quality models (AQMs) play an important role in prediction and forecasting of air pollutant concentrations which are essential components for urban air quality management. Applicability of ...advanced AQM like AERMOD is well established in developed world where sufficient input data are available. However, it is limited in developing countries due to lack of adequate and reliable data. The present study is focused to assess the urban air quality around a heritage site in Amritsar city in India using AERMOD. The performance of AERMOD is evaluated for prediction of oxide of nitrogen (NOₓ), sulphur dioxide (SO₂) and particulate matter, having the diameter ≤10 μm (PM₁₀). It is observed from the results that predicted pollutant concentrations are in satisfactory limits. The index of agreement (d) values estimated for NOₓ, SO₂ and PM₁₀ are 0.57, 0.51 and 0.50, respectively, indicating satisfactory performance of AERMOD. Similarly, other statistical descriptors also indicate its satisfactory performance in predicting the pollutant concentrations. Further, source apportionment of urban air pollutants has also been carried out using AERMOD. Besides, air quality management practices are also evaluated based on three what-if scenarios viz. (i) Introduction of battery-operated vehicles within the walled city, (ii) change in traffic movement and (iii) installation of air pollution control equipment in the free kitchen. It has been observed that after implementing the scenarios all together, PM₁₀, NOₓ and SO₂ concentrations reduce by 2.7, 9.8 and 7.0 %, respectively.
Summary
What is known and objective
Menthol has been used as a non‐opioid pain reliever since ancient times. A modern understanding of its molecular mechanism of action could form the basis for ...generating targets for discovery of novel non‐opioid analgesic drugs.
Methods
The PubMed database was queried using search words related to menthol, pain and analgesia. The results were limited to relevant preclinical studies and clinical trials and reviews published in English during the past 5 years, which yielded 31 reports. The bibliographies of these articles were sources of additional supporting articles.
Results
Menthol is a selective activator of transient receptor potential melastatin‐8 (TRPM8) channels and is also a vasoactive compound. As a topical agent, it acts as a counter‐irritant by imparting a cooling effect and by initially stimulating nociceptors and then desensitizing them. Topically applied menthol may also activate central analgesic pathways. At high concentrations, menthol may generate cold allodynia.
What is new and conclusions
Recent elucidation of TRPM8 channels has provided a molecular basis for understanding the molecular action of menthol and its ability to produce both a cooling sensation and reduction in pain associated with a wide variety of pain(ful) conditions. The more modern mechanistic understanding of menthol and its pharmacologic mechanism of action may lead to an expanded role for this substance in the search for replacements for opioid analgesics, particularly those that can be applied topically.
Recent elucidation of TRPM8 channels has provided a molecular basis for understanding the molecular action of menthol and its ability to produce both a cooling sensation and reduction in pain associated with a wide variety of pain(ful) conditions. The more modern mechanistic understanding of menthol and its pharmacologic mechanism of action may lead to an expanded role for this substance in the search for replacements for opioid analgesics, particularly those that can be applied topically.
This study aimed to assess the effects of bee pollen (BP) and/or date palm pollen (DPP) suspensions on the glycemic state, testicular dysfunctions, oxidative stress and antioxidant defense system in ...streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetes mellitus was induced by single intraperitoneal injection of STZ to overnight-fasted rats at dose of 40mg/kg body weight. After 1 week of STZ injection, diabetic rats were treated with BP and/or DPP suspensions at dose levels of 100mg/kg body weight/day for 4 weeks. The STZ-induced diabetes significantly increased blood glucose levels and testicular nitric oxide (NO) and malondialdehyde (MDA) levels parallel with disrupted testicular and pancreatic histological architecture and integrity. On the other hand, STZ-induced diabetes significantly decreased body weight, testis and pancreas weights, levels of serum insulin, testosterone, luteinizing hormone (LH) & follicle stimulating hormone (FSH) as well as sperm count, motility and viability. The administration of BP and DPP suspensions resulted in a significant recovery of the above mentioned parameters as compared to the diabetic control group. These improvements were associated with enhancement of the testicular antioxidant system manifested by an increase in the lowered glutathione content (GSH) and glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in diabetic rats as a result of treatments with BP and DPP suspensions. Thus, it can be concluded that BP and/or DPP suspensions may have potential protective role against diabetes-induced pituitary testicular axis dysfunction and testicular histological deleterious changes in association with antihyperglycemic actions via their antioxidant properties and their efficiency to improve blood insulin level and beta cell function.
Solid Ehrlich Carcinoma (SEC) is an undifferentiated tumor used in tumor studies and chemotherapy investigations.
to assess the anti-tumor potential of luteolin when used either alone or combined to ...5-fluorouracil (5-FU) against SEC.
SEC was induced in 40 female mice; they were categorized into 4 equal groups; group I (untreated SEC), group II (5-FU treated SEC), group III (luteolin treated SEC) and group IV (5-FU + luteolin treated SEC). Tumor volume and weight were calculated. P53, p21, caspase 3 and damage regulated autophagy modulator (DRAM) were assessed. Biomarkers of oxidant/antioxidant status in addition to immunohistochemistry for cylin D1 were evaluated.
Results: combined administration of luteolin and 5-FU in SEC model increased levels of p53, p21, caspase 3, DRAM and survivability while, tumor volume, weight, thioredoxin reductase one (TR1) activity and cyclin D1 expression showed the reverse with restoration of oxidant/antioxidant indices.
Conclusion: current results proved the antitumor therapeutic effects of luteolin alone or combined with 5-FU as a novel strategy for cancer therapy.
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•Solid Ehrlich Carcinoma is an undifferentiated tumor used in tumor studies and chemotherapy investigations.•P53 regulates cell cycle progression through induction of apoptosis at the G1/S checkpoint.•DRAM, a lysosomal protein, is one of p53-targeted genes and has a crucial role in autophagy process.•Luteolinco-administration with 5-FU is one of the best alternatives for cancer therapeutic strategies.•This novel formulation could possibly overcome the current limitations of 5-FU and can open a new avenue for cancer therapy.
Summary
What is known and objective
Current analgesic pharmacotherapy—opioids, non‐steroidal anti‐inflammatory drugs (NSAIDs), acetaminophen (paracetamol) and related drugs—is effective for acute ...pain, but their use is limited by adverse effects on the renal, hepatic, cardiovascular or gastrointestinal systems, or they have potential for abuse. Therefore, alternative options are desired. Compounds used in traditional medicine might offer such alternatives, but the evidence must be based on pharmacologic properties and on clinical trial data. This review summarizes the evidence for one of these: the analgesic properties of turmeric and other curcumins.
Methods
The PubMed database and other sources were searched using keywords related to turmeric, curcumin, antinociception and analgesia. Primary sources and reviews of preclinical and clinical studies were identified, assessed and summarized. Bibliographies within these sources provided additional information.
Results
Turmeric has consistently been demonstrated to produce analgesic and anti‐inflammatory effects in animal models and in clinical trials, and appears to have less serious adverse effects than many current analgesics.
What is new and conclusions
Turmeric (curcumin) appears to be a possible candidate for consideration for use as a stand‐alone analgesic, or in analgesic combinations as part of opioid‐, NSAID‐ or paracetamol (acetaminophen)‐sparing strategies.
Preclinical and clinical data suggest that turmeric (curcumin) might be a candidate for consideration for use as a stand‐alone analgesic, or in analgesic combinations as part of opioid‐, NSAID‐ or paracetamol (acetaminophen)‐sparing strategies.
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