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The aphid, Schizaphis graminum Rondani (Hemiptera: Aphididae), is one of the most destructive pests of wheat. It is responsible for significant economic losses in the agricultural sector, with an estimated 45% of wheat fields affected. Plant-based insecticides have seen a rapid increase in popularity in recent years due to their efficacy, cost-effectiveness, biodegradability, and lower toxicity compared to synthetic pesticides. The study aimed to evaluate the toxic potential of S. longipedunculata extracts against S. graminum and investigate the insect's feeding behavior on wheat. Initially macerated in methanol, the different extracts of S. longipedunculata organs were fractionated using n-hexane, chloroform, ethyl acetate, and butanol. The feeding behavior was analyzed by comparing the waveforms generated by the EPG with the control. After 72 h of treatment, the ethyl acetate fraction extracted from root had the highest toxicity against aphids, with mean 26 mortality of S. graminum at LC50 of 330 ppm; 25 mortality S. graminum at LC50 of 400 ppm for leaves; and mean 24.5 mortality S. graminum at LC50 of 540 ppm in stem bark. EPG analysis indicated that the extract fractions enhanced plant tissue resistance by significantly preventing aphid access to the phloem. The toxic effect of the botanical extracts significantly enhanced the chemical composition of the leaf medium, resulting in a drastic reduction in the number of tissue attacks by S. graminum. In summary, besides their toxicity to S. graminum, extracts of S. longipedunculata reinforce the plant's defense mechanisms, significantly reducing the S. graminum population. They also reinforce wheat's defense mechanisms. S. longipedunculata can, therefore, be used as a promising agent in the biological control of S. graminum.
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Key Clinical Message: Tarlov cysts are uncommon causes of sacral radiculopathy, with particular predilection to second and third sacral roots, requiring timely diagnosis with lumbosacral MRI, and surgical management if symptomatic. Abstract: Tarlov cysts or Type II meningeal cysts, are CSF-filled sacs located in the extradural space of the sacral spinal canal, commonly originating at the dorsal root ganglion. While they were first documented by Tarlov in 1938, their etiology remains uncertain, with theories suggesting trauma-induced bleeding or congenital abnormalities. These cysts, estimated to affect between 1% and 9% of the adult population, typically manifest as incidental findings but may lead to symptoms such as radiculopathies, sacral pain, and weakness in related sacral muscles. We present a case of a 63-year-old female presenting with recurrent left buttock pain and radiating leg discomfort. Physical examination revealed tenderness in the left buttock region, positive straight leg raise test, and minimal sensory deficits in the S1-S2 dermatomes. A provisional diagnosis of radiculopathy was made, prompting further evaluation with MRI, revealing a Tarlov cyst and absence of lumbar spinal canal stenosis or neural foraminal compromise. The patient declined intervention and was managed conservatively. This case highlights the diagnostic challenges and therapeutic considerations in managing symptomatic Tarlov cysts, emphasizing the importance of tailored treatment strategies.
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Complementary and alternative medicine-related liver injuries are increasing globally. Alternative medicine, as an inclusive healthcare practice, is widely accepted in developing and underdeveloped countries. In this context, the traditional systems of medicine in India have been at the forefront, catering to the preventive and therapeutic spectrum in the absence of conclusive evidence for benefits and lack of data on safety. Contrary to popular belief, it is evident that apart from adverse events caused by contamination and adulteration of alternative medicines, certain commonly used herbal components have inherent hepatotoxicity. This narrative review updates our current understanding and increasing publications on the liver toxicity potential of commonly used herbs in traditional Indian systems of medicine (Ayush), such as Tinospora cordifolia (Willd.) Hook.f. & Thomson (Giloy/Guduchi), Withania somnifera (L.) Dunal (Ashwagandha), Curcuma longa L. (Turmeric), and Psoralea corylifolia L. (Bakuchi/Babchi). This review also highlights the importance of the upcoming liver toxicity profiles associated with other traditional herbs used as dietary supplements, such as Centella asiatica (L.) Urb., Garcinia cambogia Desr., Cassia angustifolia Vahl (Indian senna), and Morinda citrofolia L. (Noni fruit). Fortunately, most reported liver injuries due to these herbs are self-limiting, but can lead to progressive liver dysfunction, leading to acute liver failure or acute chronic liver failure with a high mortality rate. This review also aims to provide adequate knowledge regarding herbalism in traditional practices, pertinent for medical doctors to diagnose, treat, and prevent avoidable liver disease burdens within communities, and improve public health and education.
Subject(s)
Chemical and Drug Induced Liver Injury , Complementary Therapies , Hepatitis , Liver Failure, Acute , Humans , Chemical and Drug Induced Liver Injury/etiologyABSTRACT
Protein powders, including those containing herbal and dietary supplements such as vitamins, minerals, and other natural or synthetic ingredients, can be associated with hepatotoxicity. Protein supplements are often mislabeled and deceptive in their contents. In this self-funded transparent study, we extensively analyzed popular protein supplements in India to identify potential hepatotoxic substances based on industrial standards. All products underwent extensive analysis, including total protein content, fungal aflatoxin detection, pesticide residue estimation, heavy metal quantification, steroid detection, and complete organic and inorganic profiling, according to industry standards. Most protein supplements did not meet the labeled and advertised protein content, while certain brands surpassed the stated levels, raising concerns about potential "protein/amino-spiking." In addition, the major brands contained detectable fungal toxins and pesticide residues. Furthermore, many major formulations contained harmful heavy metals such as lead and arsenic, and some featured hepatoxic herbal extracts, particularly green tea extract, turmeric, Garcinia cambogia, and Ashwagandha. Indian-made products were inferior to those manufactured by multinational companies. The presence of various potentially toxic compounds, such as cycloheptatriene, benzene derivatives, toluene, and isopropyl alcohol, within a nonstandardized and unregulated diverse ingredient mix added to the overall concern. We demonstrate that the protein-based herbal and dietary supplement industry requires stringent scrutiny, regulation, and basic safety studies before being marketed. Manufacturers must consider reducing "ingredient complexities" of their protein powders to prevent adverse interactions between herbal and nonherbal components in consumers. Manufacturers must avoid using known toxic ingredients to reduce the avoidable disease burden within the public community.
Subject(s)
Arsenic , Metals, Heavy , Humans , Metals, Heavy/analysis , Dietary Supplements/adverse effects , Vitamins , AntioxidantsABSTRACT
Recent years have witnessed security as a great concern in vehicular networks (VANET). Particularly, Denial of Service (DoS) and Distributed Denial of Service (DDoS) attacks can jeopardize the network by broadcasting a storm of packets. Correspondingly, the network resources are jammed with malicious traffic. In this connection, the existing research presented various techniques to cope with DoS and DDoS attacks. Different from those traditional approaches, this study proposes an Intelligent Intrusion Detection System (IDS) by leveraging Machine Learning (ML). The proposed IDS utilizes a publicly available dataset on the application layer for mitigating DDoS attacks. The designed ML-based IDS relies on combining both the Random Projection (RP) and Randomized Matrix Factorization (RMF) methods to achieve the best results for enhancing the detection capabilities of the IDS. This amalgamation enhances the system's detection capabilities by extracting and analyzing meaningful features from network traffic data. Experimental validation of our approach involves a comprehensive evaluation of various ML models, including Extra Tree Classifier (ETC), Logistic Regression (LR), and Random Forest (RF). Remarkably, the combined accuracy of these models yields an average system accuracy of 0.98, surpassing existing methods. Unlike conventional approaches, our proposed IDS excels in efficiency and exhibits notable performance in detecting DoS and DDoS attacks in VANET. This proficiency ensures the integrity and safety of vehicle communications. Thus, our research substantially contributes to the vehicular network security field. The presented findings establish a foundation for future advancements in securing connected vehicles.
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Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.
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Chemical and Drug Induced Liver Injury , Cholestasis , Hepatitis, Autoimmune , Liver Diseases , Humans , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/therapy , Liver Diseases/epidemiology , Liver Diseases/therapy , Cholestasis/pathology , Acute DiseaseABSTRACT
Rapid industrialization has led to an increase in cadmium pollution, a dangerously toxic heavy metal. Cadmium (Cd) is released into the environment through industrial processes and can contaminate air, water, and soil. This pollution poses a significant risk to human health and has become a pressing concern in many industrialized areas. Due to its extended half-life, it leads to a range of health problems, including hepato-nephritic toxicity, brain damage, and degenerative bone disorders. Intoxication alters various intracellular parameters, leading to inflammation, tissue injury, and oxidative stress within cells, which disrupts normal cellular functions and can eventually result in cell death. It has also been linked to the development of bone diseases such as osteoporosis. These adverse effects highlight the urgent need to address cadmium pollution and find effective solutions to mitigate its impact on human health. This article highlights the Cd-induced risks and the role of Catharanthus roseus (C. roseus) extract as a source of alternative medicine in alleviating the symptoms. Numerous herbal remedies often contain certain bioactive substances, such as polyphenols and alkaloids, which have the power to mitigate these adverse effects by acting as antioxidants and lowering oxidative cell damage. Research conducted in the field of alternative medicine has revealed its enormous potential to meet demands that may be effectively used in safeguarding humans and their environment. The point of this review is to investigate whether C. roseus extract, known for its bioactive substances, is being investigated for its potential to mitigate the harmful effects of cadmium on health. Further investigation is needed to fully understand its effectiveness. Moreover, it is important to explore the potential environmental benefits of using C. roseus extract to reduce the negative effects of Cd. This review conducted in the field of alternative medicine has revealed its enormous potential to meet demands that could have significant implications for both human health and environmental sustainability.
Subject(s)
Cadmium , Catharanthus , Humans , Cadmium/toxicity , Catharanthus/metabolism , Plant Extracts/pharmacology , Plant Extracts/metabolism , Antioxidants/metabolism , Antioxidants/pharmacologyABSTRACT
The presentation of a Morel-Lavallée lesion in the lumbosacral region following a road traffic accident is an uncommon clinical entity. Knowledge of this rare site of occurrence can help in early diagnosis and proper management.
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BACKGROUND: Liaoning score has been developed and validated to predict the risk of esophageal varices in liver cirrhosis. This study aimed to further modify the Liaoning score by combining clinical and laboratory parameters to predict the long-term outcome of cirrhotic patients. METHODS: First, 474 cirrhotic patients were retrospectively enrolled from Shenyang, China as the training cohort. Independent predictors for death were identified by competing risk analyses, and then a new prognostic model, called as modified Liaoning score, was developed. Its performance was externally validated at three centers from Fuzhou, China (n = 1944), Jinan, China (n = 485), and São Paulo, Brazil (n = 221). RESULTS: Age, total bilirubin (TBIL), albumin (ALB), serum creatinine (SCr), and Liaoning score were independently associated with death in the training cohort. Modified Liaoning score = 0.159×Liaoning score + 0.010×TBIL(µmol/L)+0.029×age(years)+0.011×SCr(µmol/L)-0.037×ALB(g/L). The area under curve of modified Liaoning score was 0.714 (95%CI = 0.655-0.773), which was higher than that of Child-Pugh score (0.707, 95%CI = 0.645-0.770), MELD score (0.687, 95%CI = 0.623-0.751), and Liaoning score (0.583, 95%CI = 0.513-0.654). A modified Liaoning score of ≥ 1.296 suggested a higher cumulative incidence of death in liver cirrhosis (p < 0.001). Modified Liaoning score still had the highest prognostic performance in Chinese and Brazilian validation cohorts. CONCLUSIONS: Modified Liaoning score can be considered for predicting the long-term outcome of cirrhotic patients.
Subject(s)
Liver Cirrhosis , Humans , Retrospective Studies , Brazil , Liver Cirrhosis/complications , Prognosis , Severity of Illness IndexABSTRACT
Background and objectives: Researchers have recently focused on the biological and synthetic effects of 1, 2, and 4-triazole fused heterocyclic molecules because they have tremendous medicinal value. The objective of the present study was to carry out the 3D QSAR evaluation on the substituted 1,2, and 4 triazole derivatives for anticancer potential using k-Nearest Neighbor-Molecular Field Analysis (kNN-MFA) method. Methods: Using the molecular design suite, a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was undertaken on a series of 4-amino-5-(pyridin3yl)-4H-1, 2, and 4-triazole-3-thiol anticancer drugs (Vlife MDS). This study used a genetic algorithm and a manual selection approach on 20 substituted 1, 2, and 4-triazole derivatives. Based on the genetic algorithm (GA), the 3D-QSAR model was generated. Statistical significance and predictive capacity were evaluated using internal and external validation. Results: The most significant model has a correlation coefficient of 0.9334 (squared correlation coefficient r2 = 0.8713), showing that biological activity and descriptors have a strong relationship. The model exhibited internal predictivity of 74.45 percent (q2 = 0.2129), external predictivity of 81.09 percent (pred r2 = 0.8417), and the smallest error term for the predictive correlation coefficient (pred r2se = 0.1255). The model revealed steric (S 1047--0.0780--0.0451S 927) and electrostatic (E 1002) data points that contribute remarkably to anticancer activity. A molecular field study demonstrates a link between the structural features of substituted triazole derivatives and their activities. Conclusion: The good-to-moderate anticancer potential of compounds confirms the significant pharmacological role of 1,2,4-triazole derivatives. These results could lead to the identification of potential chemical compounds with optimal anticancer activity and minimal side effects.
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Apple cankers are extremely destructive diseases threatening the global apple industry through direct and indirect losses. The population structure of the pathogens is of paramount significance for the development of efficient management strategies. Therefore, phenotypic, pathogenic, and genetic diversity of Diplodia seriata causing black rot canker of apple was investigated in this study. All the isolates were included for investigating the in vitro mycelial growth, conidial dimensions, and pathogenic variability on two-year-old potted apple seedlings. The ISSR approach was used to investigate the molecular diversity of D. seriata. Mycelial growth rates were found to vary significantly amongst the isolates; however, there were no major variations seen between the different geographical groupings of isolates. Pathogenicity tests revealed variations in the size of cankers among the isolates indicating the presence of virulence variability. The isolates were segregated into three virulence groups based on canker length. The Bayesian analyses of ISSR data divided the isolates into two genetic clusters. The genetic clustering of the isolates revealed no relationship with geographical origin of the isolates. Furthermore, no direct relationship of genetic clustering was observed with morphological or pathogenic variability. The ISSR primers revealed very high level of variability in D. seriata; however, no distinct populations of the pathogen existed which is an indication of high level of gene flow between the diverse geographical populations. According to our knowledge, this is the first thorough investigation on the diversity of D. seriata associated with apple black rot canker in India.
Subject(s)
Malus , Platyhelminths , Animals , Bayes Theorem , India , Genetic VariationABSTRACT
Apple cultivation is one of the most significant means of subsistence in the Kashmir region of the northwestern Himalayas. It is considered as the backbone of the region's economy. Apple cultivation in the region is dominated by a late maturing cultivar "Red Delicious" which usually on maturity causes glut in the market. In order to bring new cultivars in the cultivation, and to expand the maturity season, it is necessary to evaluate the new cultivars on fruit physico-chemical attributes which ultimately decide the market rates before recommending to farmers for cultivars adoption. Therefore, the current study was carried out to evaluate thirteen apple cultivars on physico-chemical attributes over two years, 2017 and 2018 under agro-climatic conditions of Kashmir region The results revealed that cultivars differed significantly in terms of physico-chemical properties. Cultivars with the highest and lowest values for initial fruit set, fruit drop, final fruit retention, and fruit firmness in 2017 did not follow the same trend in 2018. During 2017 and 2018, cultivar Mollie's Delicious possessed the highest fruit length (72.39 mm and 81.45 mm), fruit diameter (81.18 mm and 84.14 mm), and fruit weight (205.85 g and 247.16 g), whereas cultivar Baleman's Cider had the lowest values (50.76 mm and 52.83 mm, 60.10 mm and 62.08 mm, and 71.46 g and 86.94 g), respectively. The harvesting dates were quite spread out during both years of study. Cultivar Mollie's Delicious was harvested the earliest in both years, on August 5th, 2017 and August 8th, 2018. Cultivar Fuji Zehn Aztec was the last cultivar harvested in 2017 on October 2 and in 2018 on October 5. The maximum number of seeds per fruit was noticed in the cultivar Mollie's Delicious (8.34 and 8.71) during both 2017 and 2018, respectively. Cultivar Starkrimson had the fewest seeds per fruit in 2017 (7.11) and 2018 (7.42). Cultivar Baleman's Cider had the highest acidity in 2017 (0.63%) and 2018 (0.52%). In both 2017 (0.25%) and 2018 (0.23%), the Adam's Pearmain cultivar was the least acidic. Cultivar Allington Pippin (16.13 °Brix) and Red Gold (16.73 °Brix) had the highest TSS in 2017 and 2018, respectively, whereas Vance Delicious (12.30 °Brix) and Top Red (10.78 °Brix) had the lowest TSS in 2017 and 2018, respectively. The cultivars Mollie's Delicious and Red Gold had the highest total sugars (11.33 and 11.40%) in 2017 and 2018, respectively. Cultivar Baleman's Cider had the lowest total sugars (9.82%) in 2017 while Top Red (9.78%) in 2018. The cultivar Vance Delicious had the highest ratio of leaves to fruits in 2017 (55.44) and for Shalimar Apple-2 in 2018 (49.65). In 2017, cultivars Fuji Zehn Aztec (29.26) and Silver Spur (24.51), had the fewest leaves per fruit. The highest leaf chlorophyll content was recorded in cultivar Shireen (3.50 and 3.57 mg g-1 fresh weight) during the years 2017 and 2018, respectively. Cultivar Baleman's Cider had the lowest leaf chlorophyll content (2.15 mg g-1 fresh weight) during 2017, while cultivar Allington Pippin (2.09 mg g-1 fresh weight) had the lowest leaf chlorophyll content in 2018. The cultivars Fuji Zehn Aztec, with a yield efficiency of 0.78 kg/cm2 and Silver Spur with a yield efficiency of 1.14 kg/cm2 were the most yield efficient during the years 2017 and 2018, respectively. Cultivar Shalimar Apple-2 was least performing with yield efficiencies of 0.05 and 0.07 kg/cm2 during 2017 and 2018, respectively.The findings suggest that cultivar Mollie's Delicious commercially matures first and has the highest fruit length, diameter, and weight; hence, it can be a good option for cultivation so as to fetch the maximum price in the market when other cultivars are still maturing. Shalimar Apple-2 is precluded for cultivation due to least yield efficiency, whereas cultivars Fuji Zehn Aztec and Silver Spur are recommended to farmers for their higher yield efficiency.
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Background & Objectives: The intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing. Methods: Hydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats. Results: Based on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area. Interpretation & Conclusion: Overall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.
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During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.
Subject(s)
COVID-19 , Complementary Therapies , Hepatic Encephalopathy , Jaundice , Female , Humans , Male , Ascites/etiology , Complementary Therapies/adverse effects , COVID-19/complications , Hepatic Encephalopathy/etiology , Jaundice/complications , Liver Cirrhosis/complications , Liver Cirrhosis/therapy , Pandemics , Retrospective StudiesABSTRACT
INTRODUCTION: Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non-liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center. METHODS: A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy. RESULTS: Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in 'supposed' ultra-dilute formulations. CONCLUSION: Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not 'gentle placebos.'
Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Homeopathy , Materia Medica , Male , Humans , Middle Aged , Materia Medica/adverse effects , Homeopathy/adverse effects , Homeopathy/methods , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , India/epidemiologyABSTRACT
Lychnis coronaria, a perennial (herbaceous) belonging to Caryophyllaceae has been traditionally used for treating different complications. However, the free radical scavenging effect, anti-inflammatory activity and anticancer property of methanolic extract of this plant has not been addressed. Most importantly, the chemical constituents present in the extract of Lychnis coronaria responsible for its diverse activities have not been scrutinized till date. Here, we used a complex approach for exploring the above mentioned effects of Lychnis coronaria. We performed rigorous phytochemical screening followed by quantification of tannins, phenols, alkaloids, quinones and sterols from the extract. Moreover we employed in vitro DPPH, ABTS , FRAP assay, albumin denaturation inhibition experiment, MTT assay, high resolution liquid chromatography mass spectrometry for measurng the reactive oxygen species quenching, anti-inflammatory and anticancer strength of Lychnis coronaria and for identifying the possible bioactive molecules. We identified two novel molecules panaxynol (polyacetylenic alcohol) and norharman (9H-Pyrido [3, 4-B] indole) following rigorous analysis of the extract. Following this, the binding affinity of these molecules was estimated using human cyclooxygenase (COX)-2 enzyme as target. Among the constituents of Lychnis coronaria norharman manifested stronger binding towards COX-2 compared to panaxynol. Most importantly, norharman showed high stability in the groove of COX2 as confirmed by molecular dynamics simulation. Collectively, Lychnis coronaria manifested free radical neutralizing, inflammation soothing and anticancer effect in concentration dependent manner and thus may serve as a promising phytotherapeutic in future.Communicated by Ramaswamy H. Sarma.
Subject(s)
Lychnis , Plant Extracts , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/chemistry , Phytochemicals/pharmacology , Chromatography, Liquid , Free Radicals , Mass Spectrometry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistryABSTRACT
Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl2), a Cu(II) compound, on various parameters of oxidative stress, cellular metabolism, and DNA integrity in the rat kidney. This was done to delineate the molecular mechanism of Cu(II) toxicity. Adult male rats were randomly divided into five groups. Animals in four CuCl2-treated groups were separately administered single acute oral dose of CuCl2 at 5, 15, 30, and 40 mg/kg body weight. Animals in the fifth group were not given CuCl2 and served as the control. All rats were sacrificed 24 h after the dose of CuCl2 and their kidneys removed. CuCl2 administration led to significant alterations in enzymatic and non-enzymatic parameters of oxidative stress. It changed the activities of metabolic and membrane bound enzymes and also decreased the activities of brush border membrane enzymes. CuCl2 treatment dose-dependently enhanced DNA damage and DNA-protein crosslinking in renal cells, when compared to the control group. The administration of CuCl2 also resulted in marked morphological changes in the kidney, with more prominent alterations at higher doses of CuCl2. These results clearly show that CuCl2 impairs the antioxidant defense system resulting in oxidative damage to the kidney.
Subject(s)
Antioxidants , Copper , Humans , Male , Rats , Animals , Antioxidants/metabolism , Copper/metabolism , Chlorides/pharmacology , Oxidative Stress , Kidney/metabolism , Administration, Oral , DNA DamageABSTRACT
The advancement in cancer research using high throughput technology and artificial intelligence (AI) is gaining momentum to improve disease diagnosis and targeted therapy. However, the complex and imbalanced data with high dimensionality pose significant challenges for computational approaches and multi-omics data analysis. This study focuses on predicting skin cancer and analyzing overall survival probability. We employ the Kaplan-Meier estimator and Cox proportional hazards regression model, utilizing high-throughput machine learning (ML)-based ensemble methods. Our proposed ML-based ensemble techniques are applied to a publicly available dataset from the ICGC Data Portal, specifically targeting skin cutaneous melanoma cancers (SKCM). We used eight baseline classifiers, namely, random forest (RF), decision tree (DT), gradient boosting (GB), AdaBoost, Gaussian naïve Bayes (GNB), extra tree (ET), logistic regression (LR), and light gradient boosting machine (Light GBM or LGBM). The study evaluated the performance of the proposed ensemble methods and survival analysis on SKCM. The proposed methods demonstrated promising results, outperforming other algorithms and models in terms of accuracy compared to traditional methods. Specifically, the RF classifier exhibited outstanding precision results. Additionally, four different ensemble methods (stacking, bagging, boosting, and voting) were created and trained to achieve optimal results. The performance was evaluated and interpreted using accuracy, precision, recall, F1 score, confusion matrix, and ROC curves, where the voting method achieved a promising accuracy of 99%. On the other hand, the RF classifier achieved an outstanding accuracy of 99%, which exhibits the best performance. We compared our proposed study with the existing state-of-the-art techniques and found significant improvements in several key aspects. Our approach not only demonstrated superior performance in terms of accuracy but also showcased remarkable efficiency. Thus, this research work contributes to diagnosing SKCM with high accuracy.
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The root-knot nematode Meloidogyne incognita is one of the most damaging plant-parasitic nematodes and is responsible for significant crop losses worldwide. Rising human health and environmental concerns have led to the withdrawal of commonly used chemical nematicides. There has been a tremendous demand for eco-friendly bio-nematicides with beneficial properties to the nematode hosting plants, which encourages the need for alternative nematode management practices. The current study was undertaken to determine the nematicidal potential of cotton seed cake (CSC) against second-stage juvenile (J2) hatching, J2 mortality, and J2 penetration of M. incognita in tomato plants in vitro. J2s and egg masses of M. incognita were exposed to four concentrations (250, 500, 750, and 1000 mg/L) of CSC extracts. The higher J2 mortality and inhibition of J2 hatching were found at 1000 mg/L, while the least effective result was observed at 250 mg/L of the CSC extract. The CSC extract applied with the concentrations mentioned above also showed inhibition of J2 penetration in tomato roots; 1000 mg/L showed the highest inhibition of penetration, while 250 mg/L displayed the least inhibition. Using gas chromatography-mass spectroscopy, we identified 11 compounds, out of which 9,12-Octadecadienoic acid, Hexadecanoic acid, and Tetradecanoic acid were found as major compounds. Subsequently, in silico molecular docking was conducted to confirm the nematicidal behavior of CSC based on binding interactions of the above three major compounds with the targeted protein acetylcholine esterase (AChE) of M. incognita. The values of binding free energy are -5.3, -4.5, and -4.9 kcal/mol, observed for 9,12-Octadecadienoic acid, n-Hexadecanoic acid, and Tetradecanoic acid, respectively, suggesting that 9,12-Octadecadienoic acid binds with the receptor AChE more efficiently than the other two ligands. This study indicates that CSC has nematicidal potential that can be used to control M. incognita for sustainable agriculture.
ABSTRACT
Globally, people are highly affected by Cadmium (Cd), the most hazardous heavy metal. It has been implicated in various pathogeneses. Oxidative stress may be one the main reasons for Cd-induced disorders in the body. This article investigates the protective ability of Catharanthus roseus (CR) extract on oxidative stress in the kidney and liver of rats exposed to Cd. After 21 days, a significant increase in MDA concentration (6.81 ± 0.05), (6.64 ± 0.03) was observed in Cd-treated groups compared to the control (5.54 ± 0.02), (5.39 ± 0.04) for the kidney and liver, respectively, while significant changes were observed in the haematological parameters. Antioxidant enzymes, GPx, CAT, and SOD showed a significant decrease in their activity. We established that increasing the concentration of Cd in the presence of H2O2 was able to cause stand scission in pBR322 plasmid DNA, which may be due to the mediation of ROS generated in the process. The antioxidant ability of CR extract was tested in DPPH and H2O2 scavenging assay, depicted by the increase in the percentage inhibition. Upon treatment of CR extract to rats, MDA concentration was decreased for the kidney and liver compared to the Cd-treated groups. This was again confirmed by comet assay of both tissues, where the degree of cellular DNA breakage caused by Cd toxicity decreased significantly upon treatment with CR extract. Overall, the results suggest that Cd plays a major role as an effector metal ion, causing a decrease in the concentration and activity of AO enzymes and enhanced lipid peroxidation. ROS production resulted in oxidative DNA damage within the cell, whereas CR extract showed potential antioxidant activity against ROS-mediated DNA damage induced by Cd poisoning.