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Objectives: A monoterpene alpha-pinene possesses anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Here, we investigated the effect of alpha-pinene on molecular, biochemical, and histological changes induced by carbon tetrachloride (CCl 4 ) in the liver of male Wistar rats., Materials and Methods: Animals were divided into four groups: Control, Pinene, CCl 4 , and CCl 4 .Pinene. Pinene and CCl 4 .Pinene groups were given alpha-pinene (50 mg/kg/day) through intraperitoneal (IP) injections for six consecutive weeks. CCl 4 and CCl 4 .Pinene groups received IP injections of CCl 4 (2 ml/kg twice weekly for six consecutive weeks)., Results: The results revealed that alpha-pinene inhibited enhancing liver enzyme AST ( P <0.001), ALT ( P <0.001), ALP ( P <0.01), and GGT ( P <0.001) activity in CCl 4 .Pinene rats. It reduced malondialdehyde ( P <0.05) and nitric oxide ( P <0.05) levels and increased the catalase enzyme activity ( P <0.05) and glutathione levels ( P <0.01) in the liver. Likewise, alpha-pinene suppressed proinflammatory and profibrotic gene expression and prevented significant histological damage and collagen deposition in the liver of these animals. Also, alpha-pinene reduced the expression of TLR4 ( P <0.01), NF-κB ( P <0.05), PI3K ( P <0.05), Akt ( P <0.05), mTOR ( P <0.01), TGF-β1 ( P <0.01), and Smad3 ( P <0.01) in the liver of rats receiving CCl 4 ., Conclusion: We concluded that alpha-pinene reduced CCl 4 -induced liver fibrosis by lowering oxidative stress, suppressing liver inflammation, and inhibiting TLR4/NF-κB, TGF-β/Smad3, and PI3K/Akt/mTOR signaling pathways. Consequently, alpha-pinene may have potential therapeutic value in treating liver diseases., Competing Interests: The authors declare that they have no conflicts of interest., (2025. This work is openly licensed via CC BY 4.0.) more...

Objectives: Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl 4 ., Materials and Methods: CCl 4 was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period., Results: CCl 4 increased the level of malondialdehyde ( P <0.01 in the kidney and P <0.001 in the testis) and nitric oxide ( P <0.001 in the kidney and P <0.01 in the testis) and decreased the levels of glutathione ( P <0.05) in the kidneys and testicles of rats. CCl 4 also reduced the catalase enzyme activity in the kidneys ( P <0.05) but did not affect its activity in the testis. In addition, CCl 4 enhanced the mRNA expression of TNF-α ( P <0.01), nuclear factor-κB (P<0.05), and Bax ( P <0.05 in the kidney and P <0.01 in the testis) and decreased the expression of Bcl-2 ( P <0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl 4 ., Conclusion: Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl 4 ., Competing Interests: None. more...

Backgrounds: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by a clonal accumulation of mature apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a variable clinical outcome. Here, we present a review of currently known (epi)genetic alterations that are related to the etiology, progression and chemo-refractoriness of CLL. Relevant literature was identified through a PubMed search (1994-2014) of English-language papers using the terms CLL, signaling pathway, cytogenetic abnormality, somatic mutation, epigenetic alteration and micro-RNA., Results: CLL is characterized by the presence of gross chromosomal abnormalities, epigenetic alterations, micro-RNA expression alterations, immunoglobulin heavy chain gene mutations and other genetic lesions. The expression of unmutated immunoglobulin heavy chain variable region (IGHV) genes, ZAP-70 and CD38 proteins, the occurrence of chromosomal abnormalities such as 17p and 11q deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been associated with a poor prognosis. In addition, mutations in tumor suppressor genes, such as TP53 and ATM, have been associated with refractoriness to conventional chemotherapeutic agents. Micro-RNA expression alterations and aberrant methylation patterns in genes that are specifically deregulated in CLL, including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked to distinct clinical parameters., Conclusions: Specific chromosomal abnormalities and gene mutations may serve as diagnostic and prognostic indicators for disease progression and survival. The identification of these anomalies by state-of-the-art molecular (cyto)genetic techniques such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), single nucleotide polymorphism (SNP) microarray-based genomic profiling and next-generation sequencing (NGS) can be of paramount help for the clinical management of these patients, including optimal treatment design. The efficacy of novel therapeutics should to be tested according to the presence of these molecular lesions in CLL patients. more...