Carum carvi Modulates Acetaminophen-Induced Hepatotoxicity: Effects on TNF-α, NF-κB, and Caspases

Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent manner. Our results also confirm that liver toxicity associated with paracetamol, such as depletion of reduced glutathione and antioxidant enzyme levels, as well as induction of cytochrome P450, oxidative stress, apoptosis, and inflammatory cytokines, was efficiently restored by Carum carvi treatment in rats. Moreover, the expression of redox-sensitive transcription factors, namely, NF-κB and TNF-α levels, was also modulated by Carum carvi in the rats. In summary, our study confirms that Carum carvi inhibits inflammation and oxidative stress, thereby protecting liver cells from paracetamol prompted hepatotoxicity

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Can the Fisher Effect Theory Work in Pakistan?

This paper examines the relationship between the stock market and inflation rate in Pakistan, using the bootstrap Granger full-sample causality test and sub-sample rolling window estimation to test whether the results support the Fisher hypothesis in Pakistan. The empirical result of full sample size shows the unidirectional causality between the stock market and inflation rate. It further shows that in the presence of structural changes, full sample relationship is unstable and unreliable. We use the rolling window estimation considering the time-varying characteristics and conclude bidirectional causality between the inflation rate and stock market in the different sub-sample. The findings are inconsistent with Fisher hypothesis. The conclusion that Inflation rate and the stock market have no positive long-term relationship; the stock market does not offer a hedge against an inflation rate so the policy maker should take measures to balance the tradeoff between the stock market and inflation rate in the short run

How Often Does the Exchange Rate Granger Cause the Stock Market in Pakistan? A Bootstrap Rolling Window Approach

This paper investigates the causal link between the stock market (SM) and the exchange rate (EXR) in Pakistan, using the bootstrap Granger causality and sub-sample rolling window estimation. The full sample Granger causality test indicates no causality between the SM and the EXR. The stability of the parameters is examined by taking into the account structural changes for individual series as well as the VAR. The full sample Granger test shows the absence of causality. The rolling window approach shows the uni-directional positive and negative relationship between the SM and the EXR. The study gives some suggestions to the government and policy makers that a well-coordinated policy implementation and execution regarding the SM and the EXR are crucial in attracting foreign investors and developing a sound financial system in the country complementary to the development of the econom

Role of CPEC in Development of Trade, Transport and Economy of Pakistan

The objectives of the study were to measure the efficiency in trade and transport through China Pakistan Economic Corridor (CPEC) and to ascertain efficiency in trade and economic development through developed transport infrastructures. The present study was conducted in Peshawar, Pakistan. The data was collected from the relevant developing sectors and stakeholders through CPEC including investors of Khyber Pakhtunkhwa Chamber of Commerce and Peshawar Railway Station track employees. Majority of bi-variate analysis through chi-square test result showed that there was a strong and significant association between the project of CPEC and efficiency in trade and transport in terms of economy. Similarly, a strong and significant association was found between the development of transport routes through CPEC and smooth transportation of goods and services. Furthermore, a strong and significant association was found between CPEC project and improvement in travelling potential. Similarly, a significant association was found between development in transport infrastructure and fastness and reliability in business travelling. In the same way, a significant association was found between CPEC and increase in the geographical size of the labour market. As in the chain, a strong and significant association was found between the development of transport infrastructures through CPEC and increase in labour force productivity along with an increase in the range of choice of individual and firms. This could come true that CPEC as a project would ensure smooth efficiency transportation of trade goods and services in terms of reducing time distance and cost. CPEC as a project should not be only limited to economic activities, rather it should contribute to the overall socio-economic development of the region

<i>Carum carvi</i> Modulates Acetaminophen-Induced Hepatotoxicity: Effects on TNF-α, NF-κB, and Caspases

Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent manner. Our results also confirm that liver toxicity associated with paracetamol, such as depletion of reduced glutathione and antioxidant enzyme levels, as well as induction of cytochrome P450, oxidative stress, apoptosis, and inflammatory cytokines, was efficiently restored by Carum carvi treatment in rats. Moreover, the expression of redox-sensitive transcription factors, namely, NF-κB and TNF-α levels, was also modulated by Carum carvi in the rats. In summary, our study confirms that Carum carvi inhibits inflammation and oxidative stress, thereby protecting liver cells from paracetamol prompted hepatotoxicity

Correction: Ali, A., et al. Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach. Vet. Sci. 2020, 7, 129

The authors wish to make the following corrections to this paper [...

Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host homologous, and unique metabolic proteins in the complete proteome of selected pathogens. Among these therapeutic target proteins, three were excluded due to the presence in host gut metagenome, eleven were found to be highly potential drug targets, while only one was found as a potential vaccine candidate against TBPs. The present study may provide a foundation to design potential drug targets and vaccine candidates for the effective control of infections caused by TBPs