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Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Inflamação/tratamento farmacológicoRESUMO
Pre-mRNA processing factor 4B (PRP4) promotes pre-mRNA splicing and signal transduction. Recent studies have shown that PRP4 modulates the assembly of actin cytoskeleton in cancer cells and induces epithelial-mesenchymal transition (EMT) and drug resistance. PRP4 displays kinase domain-like cyclin-dependent kinases and mitogen-activated protein kinases, making it capable of phosphorylating p53 and other target proteins. In the current study, we report that PRP4 induces drug resistance and EMT via direct binding to the p53 protein, inducing its phosphorylation. Moreover, PRP4 overexpression activates the transcription of miR-210 in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner, which activates p53. The involvement of miR-210 in the activation of p53 was confirmed by utilizing si-miR210. si-miR210 blocked the PRP4-activated cell survival pathways and reversed the PRP4-induced EMT phenotype. Moreover, we used deferoxamine as a hypoxia-mimetic agent, and si-HIF to silence HIF-1α. This procedure demonstrated that PRP4-induced EMT and drug resistance emerged in response to consecutive activation of HIF-1α, miR-210, and p53 by PRP4 overexpression. Collectively, our findings suggest that the PRP4 contributes to EMT and drug resistance induction via direct interactions with p53 and actions that promote upregulation of HIF-1α and miR-210. We conclude that PRP4 is an essential factor promoting cancer development and progression. Specific PRP4 inhibition could benefit patients with colon cancer.
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Neoplasias do Colo , MicroRNAs , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Resistência a Medicamentos , Transição Epitelial-Mesenquimal/genética , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases , Precursores de RNA/metabolismo , Ribonucleoproteína Nuclear Pequena U4-U6 , Proteína Supressora de Tumor p53/genéticaRESUMO
Pre-mRNA processing factor 4B (PRP4) has previously been shown to induce epithelial-mesenchymal transition (EMT) and drug resistance in cancer cell lines. As melanin plays an important photoprotective role in the risk of sun-induced skin cancers, we have investigated whether PRP4 can induce drug resistance and regulate melanin biosynthesis in a murine melanoma (B16F10) cell line. Cells were incubated with a crucial melanogenesis stimulator, alpha-melanocyte-stimulating hormone, followed by transfection with PRP4. This resulted in the inhibition of the production of melanin via the downregulation of adenylyl cyclase-cyclic adenosine 3',5'-monophosphate (AC)-(cAMP)-tyrosinase synthesis signaling pathway. Inhibition of melanin production by PRP4 leads to the promotion of carcinogenesis and induced drug resistance in B16F10 cells. Additionally, PRP4 overexpression upregulated the expression of ß-arrestin 1 and desensitized the extracellular calcium-sensing receptor (CaSR), which in turn, inhibited the influx of extracellular Ca2+ ions. The decreased influx of Ca2+ was confirmed by a decreased expression level of calmodulin. We have demonstrated that transient receptor potential cation channel subfamily C member 1 was involved in the influx of CaSR-induced Ca2+ via a decreasing level of its expression. Furthermore, PRP4 overexpression downregulated the expression of AC, decreased the synthesis of cAMP, and modulated the actin cytoskeleton by inhibiting the expression of Ras homolog family member A (RhoA). Our investigation suggests that PRP4 inhibits the production of melanin in B16F10 cells, blocks the influx of Ca2+ through desensitization of CaSR, and modulates the actin cytoskeleton through downregulating the AC-cAMP pathway; taken together, these observations collectively lead to the promotion of skin carcinogenesis.
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Citoesqueleto de Actina/metabolismo , Cálcio/metabolismo , Melaninas/biossíntese , Ribonucleoproteína Nuclear Pequena U4-U6/metabolismo , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/metabolismo , Animais , Antineoplásicos , Calmodulina/genética , Calmodulina/metabolismo , Proteínas de Transporte , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Espaço Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Espaço Intracelular/metabolismo , Melanoma Experimental , Camundongos , Ligação Proteica , Ribonucleoproteína Nuclear Pequena U4-U6/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/patologiaRESUMO
Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.
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Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanomedicina Teranóstica , Administração Intranasal , Animais , Barreira Hematoencefálica/metabolismo , Doenças do Sistema Nervoso Central/tratamento farmacológico , Vias de Administração de Medicamentos , Portadores de Fármacos , Humanos , Nanopartículas/química , PermeabilidadeRESUMO
OBJECTIVE: The Jeju native pig (JNP) found on the Jeju Island of Korea is a unique black pig known for high-quality meat. To investigate the genetic uniqueness of JNP, we analyzed the selection signature of the JNP in comparison to commercial pigs such as Berkshire and Yorkshire pigs. METHODS: We surveyed the genetic diversity to identify the genetic stability of the JNP, using the linkage disequilibrium method. A selective sweep of the JNP was performed to identify the selection signatures. To do so, the population differentiation measure, Weir-Cockerham's Fst was utilized. This statistic directly measures the population differentiation at the variant level. Additionally, we investigated the gene ontologies (GOs) and genetic features. RESULTS: Compared to the Berkshire and Yorkshire pigs, the JNP had lower genetic diversity in terms of linkage disequilibrium decays. We summarized the selection signatures of the JNP as GO. In the JNP and Berkshire pigs, the most enriched GO terms were epithelium development and neuron-related. Considering the JNP and Yorkshire pigs, cellular response to oxygen-containing compound and generation of neurons were the most enriched GO. CONCLUSION: The selection signatures of the JNP were identified through the population differentiation statistic. The genes with possible selection signatures are expected to play a role in JNP's unique pork quality.
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Cell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho-associated protein kinase (ROCK), LIM-Kinase (LIMK), and cofilin. Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. In this study, we discovered that PRP4 over-expression in HCT116 colon cancer cells induces cofilin dephosphorylation by inhibiting the Rho-ROCK-LIMK-cofilin pathway. Two-dimensional gel electrophoresis, and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4-transfected HCT116 cells. The presence of PRP4 increased the expression of PP1A both at the mRNA and protein levels, which possibly activated cofilin through dephosphorylation and subsequently modulated the cell actin cytoskeleton. Furthermore, we found that PRP4 over-expression did not induce cofilin dephosphorylation in the presence of okadaic acid, a potent phosphatase inhibitor. Moreover, we discovered that PRP4 over-expression in HCT116 cells induced dephosphorylation of migration and invasion inhibitory protein (MIIP), and down-regulation of E-cadherin protein levels, which were further restored by the presence of okadaic acid. These findings indicate a possible molecular mechanism of PRP4-induced actin cytoskeleton remodeling and epithelial-mesenchymal transition, and make PRP4 an important target in colon cancer.
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Citoesqueleto de Actina/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Transição Epitelial-Mesenquimal/genética , Proteínas Serina-Treonina Quinases/fisiologia , Ribonucleoproteína Nuclear Pequena U4-U6/fisiologia , Citoesqueleto de Actina/genética , Adesão Celular/genética , Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Citoesqueleto/genética , Citoesqueleto/metabolismo , Células HCT116 , Humanos , Quinases Lim/metabolismo , Invasividade Neoplásica , Proteínas Serina-Treonina Quinases/metabolismo , Ribonucleoproteína Nuclear Pequena U4-U6/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C. These compounds have the ability to induce apoptosis by activating pro-apoptotic proteins and the caspase cascade, and reduced the expression of anti-apoptotic proteins such as B-cell lymphoma 2 and B-cell lymphoma-extra-large. Interaction with multiple molecular targets and cytotoxic effects, these two compounds are favorable candidates for treating various chronic inflammatory diseases such as cancers (prostate, breast, leukemia, cervical, and myeloma), rheumatoid arthritis, diabetic retinopathy, hepatic fibrosis, osteoclastogenesis, allergy, and Alzheimer's disease. We have summarized the preliminary studies regarding the biological effects of decursin and DA. In this review, we will also highlight the functions of coumarin compounds that can be translated to a clinical practice for the treatment and prevention of various inflammatory ailments.
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Anti-Inflamatórios , Benzopiranos , Butiratos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Butiratos/farmacologia , Butiratos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Citocromo P-450 CYP2A6/antagonistas & inibidores , Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2J2 , Sistema Enzimático do Citocromo P-450/metabolismo , HumanosRESUMO
Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1ß and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1ß and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers.
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Anti-Inflamatórios/farmacologia , Benzopiranos/farmacologia , Butiratos/farmacologia , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/citologia , NF-kappa B/metabolismo , Animais , Polaridade Celular/efeitos dos fármacos , Citocinas/metabolismo , Células HL-60 , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Ésteres de Forbol/farmacologia , Transporte Proteico/efeitos dos fármacos , Células RAW 264.7RESUMO
Milk-related traits (milk yield, fat and protein) have been crucial to selection of Holstein. It is essential to find the current selection trends of Holstein. Despite this, uncovering the current trends of selection have been ignored in previous studies. We suggest a new formula to detect the current selection trends based on single nucleotide polymorphisms (SNP). This suggestion is based on the best linear unbiased prediction (BLUP) and the Fisher's fundamental theorem of natural selection both of which are trait-dependent. Fisher's theorem links the additive genetic variance to the selection coefficient. For Holstein milk production traits, we estimated the additive genetic variance using SNP effect from BLUP and selection coefficients based on genetic variance to search highly selective SNPs. Through these processes, we identified significantly selective SNPs. The number of genes containing highly selective SNPs with p-value <0.01 (nearly top 1% SNPs) in all traits and p-value <0.001 (nearly top 0.1%) in any traits was 14. They are phosphodiesterase 4B (PDE4B), serine/threonine kinase 40 (STK40), collagen, type XI, alpha 1 (COL11A1), ephrin-A1 (EFNA1), netrin 4 (NTN4), neuron specific gene family member 1 (NSG1), estrogen receptor 1 (ESR1), neurexin 3 (NRXN3), spectrin, beta, non-erythrocytic 1 (SPTBN1), ADP-ribosylation factor interacting protein 1 (ARFIP1), mutL homolog 1 (MLH1), transmembrane channel-like 7 (TMC7), carboxypeptidase X, member 2 (CPXM2) and ADAM metallopeptidase domain 12 (ADAM12). These genes may be important for future artificial selection trends. Also, we found that the SNP effect predicted from BLUP was the key factor to determine the expected current selection coefficient of SNP. Under Hardy-Weinberg equilibrium of SNP markers in current generation, the selection coefficient is equivalent to 2*SNP effect.
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The missing heritability has been a major problem in the analysis of best linear unbiased prediction (BLUP). We introduced the traditional genome-wide association study (GWAS) into the BLUP to improve the heritability estimation. We analyzed eight pork quality traits of the Berkshire breeds using GWAS and BLUP. GWAS detects the putative quantitative trait loci regions given traits. The single nucleotide polymorphisms (SNPs) were obtained using GWAS results with p value <0.01. BLUP analyzed with significant SNPs was much more accurate than that with total genotyped SNPs in terms of narrow-sense heritability. It implies that genomic estimated breeding values (GEBVs) of pork quality traits can be calculated by BLUP via GWAS. The GWAS model was the linear regression using PLINK and BLUP model was the G-BLUP and SNP-GBLUP. The SNP-GBLUP uses SNP-SNP relationship matrix. The BLUP analysis using preprocessing of GWAS can be one of the possible alternatives of solving the missing heritability problem and it can provide alternative BLUP method which can find more accurate GEBVs.
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Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble systemic drugs. Curcumin, a yellow pigment isolated from turmeric, possesses a wide range of pharmacological activities, including anticancer effects. The anticancer potential of curcumin is mediated through the inhibition and modulation of several intracellular signaling pathways, as confirmed in various in vitro and in vivo cancer studies. However, clinical application of dietary curcumin for the treatment of cancer and other chronic diseases have been hindered by poor bioavailability, due to low systemic solubility as well as rapid metabolism and elimination from the body. Different techniques for sustained and efficient curcumin delivery, including nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles are the focus of this study. Previous studies have shown that nanocurcumin has improved anticancer effects as compared to normal curcumin formulations. Among nanoformulations, few composite nanosystems have the simultaneous properties of therapeutic activity and multifunctional nanoparticles as enhanced image contrast agents. We also address the challenges to the development of nanocurcumin delivery platforms by enhancing a steady aqueous dispersion state. Further studies are needed using preclinical and clinical cancer models to recommend nanocurcumin as a drug of choice for cancer therapy.
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Curcumina/administração & dosagem , Curcumina/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Absorção , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Cristalização/métodos , Difusão , Composição de Medicamentos/métodos , Desenho de Fármacos , Humanos , Nanocápsulas/efeitos da radiaçãoRESUMO
Traditionally, the p-value is the criterion for the cutoff threshold to determine significant markers in genome-wide association studies (GWASs). Choosing the best subset of markers for the best linear unbiased prediction (BLUP) for improved prediction ability (PA) has become an interesting issue. However, when dealing with many traits having the same marker information, the p-values' themselves cannot be used as an obvious solution for having a confidence in GWAS and BLUP. We thus suggest a genomic estimated breeding value-assisted reduction method of the single nucleotide polymorphism (SNP) set (GARS) to address these difficulties. GARS is a BLUP-based SNP set decision presentation. The samples were Landrace pigs and the traits used were back fat thickness (BF) and daily weight gain (DWG). The prediction abilities (PAs) for BF and DWG for the entire SNP set were 0.8 and 0.8, respectively. By using the correlation between genomic estimated breeding values (GEBVs) and phenotypic values, selecting the cutoff threshold in GWAS and the best SNP subsets in BLUP was plausible as defined by GARS method. 6,000 SNPs in BF and 4,000 SNPs in DWG were considered as adequate thresholds. Gene Ontology (GO) analysis using the GARS results of the BF indicated neuron projection development as the notable GO term, whereas for the DWG, the main GO terms were nervous system development and cell adhesion.
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The cell cycle has the capacity to safeguard the cell's DNA from damage. Thus, cell cycle arrest can allow tumor cells to investigate their own DNA repair processes. Cancer cells become extremely reliant on G1-phase cyclin-dependent kinases due to mutated oncogenes and deactivated tumor suppressors, producing replication stress and DNA damage during the S phase and destroying checkpoints that facilitate progression through the S/G2/M phase. DNA damage checkpoints activate DNA repair pathways to prevent cell proliferation, which occurs when the genome is damaged. However, research on how cells recommence division after a DNA lesion-induced arrest is insufficient which is merely the result of cancer cells' susceptibility to cell cycle arrest. For example, defects in the G1 arrest checkpoint may cause a cancer cell to proliferate more aggressively, and attempts to fix these complications may cause the cell to grow more slowly and eventually die. Defects in the G2-M arrest checkpoint may enable a damaged cell to enter mitosis and suffer apoptosis, and attempts to boost the effectiveness of chemotherapy may increase its cytotoxicity. Alternatively, attempts to promote G2-M arrest have also been linked to increased apoptosis in the laboratory. Furthermore, variables, such as hyperthermia, contact inhibition, nucleotide shortage, mitotic spindle damage, and resting phase effects, and DNA replication inhibitors add together to halt the cell cycle. In this review, we look at how nucleotide excision repair, MMR, and other variables, such as DNA replication inhibitors, hyperthermia, and contact inhibition, contribute to the outlined processes and functional capacities that cause cell cycle arrest.
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Apoptose , Hipertermia Induzida , Inibição de Contato , Pontos de Checagem da Fase G2 do Ciclo Celular , Linhagem Celular Tumoral , Ciclo Celular , Divisão Celular , Reparo do DNA , Dano ao DNA , DNARESUMO
Cancer is a complex and multistage disease that affects various intracellular pathways, leading to rapid cell proliferation, angiogenesis, cell motility, and migration, supported by antiapoptotic mechanisms. Chemoprevention is a new strategy to counteract cancer; to either prevent its incidence or suppress its progression. In this strategy, chemopreventive agents target molecules involved in multiple pathways of cancer initiation and progression. Nrf2, STAT3, and Src are promising molecular candidates that could be targeted for chemoprevention. Nrf2 is involved in the expression of antioxidant and phase II metabolizing enzymes, which have direct antiproliferative action as well as indirect activities of reducing oxidative stress and eliminating carcinogens. Similarly, its cross-talk with NF-κB has great anti-inflammatory potential, which can be utilized in inflammation-induced/associated cancers. STAT3, on the other hand, is involved in multiple pathways of cancer initiation and progression. Activation, phosphorylation, dimerization, and nuclear translocation are associated with tumor cell proliferation and angiogenesis. Src, being the first oncogene to be discovered, is important due to its convergence with many upstream stimuli, its cross-talk with other potential molecular targets, such as STAT3, and its ability to modify the cell cytoskeleton, making it important in cancer invasion and metastasis. Therefore, the development of natural/synthetic molecules and/or design of a regimen that can reduce oxidative stress and inflammation in the tumor microenvironment and stop multiple cellular targets in cancer to stop its initiation or retard its progression can form newer chemopreventive agents.
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Although conserving native pig breeds is important in Korea, research on the genomic aspects to identify breed-specific variations in native pig breeds is uncommon. Single nucleotide polymorphisms (SNPs) can be a powerful source for identifying breed-specific variants. We used whole genome sequencing data, including Jeju Native Pig (JNP), Korean Native Pig (KNP), Korean Wild Boar (KWB), and other western commercial pig breeds to determine native pig breed-specific SNPs. Furthermore, the goal was not only to determine the genomic specificity of native pig breeds but also to identify SNPs that carry breed-specific information (breed-informative SNPs) that can be related to breed characteristics. The representative characteristics of native pigs are their unique meat quality and disease resistance. We surveyed the gene ontology (GO) of native pigs with breed-specific SNPs. Examining the genes associated with GO may contribute to revealing the reasons for the unique characteristics of native pig breeds. The enriched GOs terms were neuron projection development, cell surface receptor signaling pathway, ion homeostasis in JNP, cell adhesion and wound healing in KNP, and DNA repair and reproduction in KWB. We expect that this study of breed-specific SNPs will enable us to gain a deeper understanding of native pigs in Korea.
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Malaria is a parasitic infection caused by bites from Plasmodium falciparum (P. falciparum)-infected mosquitoes with a present scale of symptoms ranging from moderate fever to neurological disorders. P. falciparum is the most lethal of the five strains of malaria, and is a major case of morbidity and mortality in endemic regions. Recent advancements in malaria diagnostic tools and prevention strategies have improved conjugation antimalarial therapies using fumigation and long-lasting insecticidal sprays, thus lowering malarial infections. Declines in the total number of infected individuals have been correlated with antimalarial drugs. Despite this, malaria remains a major health threat, affecting more than 30 million men, women, and children around the globe, and 20 percent of all children around the globe have malaria parasites in their blood. To overcome this life-threatening condition, novel therapeutic strategies, including immunization, are urgently needed to tackle this infection around the world. In line with this, the development of the RTS, S vaccine was a significant step forward in the fight against malaria. RTS, S is a vaccine for P. falciparum in which R specifies central repeat units, T the T-cell epitopes, and S indicates surface antigen. The RTS, S/AS01 malarial vaccine was synthesized and screened in several clinical trials between 2009 and 2014, involving thousands of young children in seven African countries, showing that children who received the vaccine did not suffer from severe malaria. Mosquirix™ was approved by the World Health Organization in 2021, indicating it to be safe and advocating its integration into routine immunization programs and existing malaria control measures. This paper examines the various stages of the vaccine's development, including the evaluation of its immunogenicity and efficacy on the basis of a total of 2.3 million administered doses through a routine immunization program. The protection and effectiveness provided by the vaccine are strong, and evidence shows that it can be effectively delivered through the routine child immunization platform. The economic cost of the vaccine remains to be considered.
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Cancer is one of the most common causes of death globally. Despite extensive research and considerable advances in cancer therapy, the fundamentals of the disease remain unclear. Understanding the key signaling mechanisms that cause cancer cell malignancy may help to uncover new pharmaco-targets. Cyclic adenosine monophosphate (cAMP) regulates various biological functions, including those in malignant cells. Understanding intracellular second messenger pathways is crucial for identifying downstream proteins involved in cancer growth and development. cAMP regulates cell signaling and a variety of physiological and pathological activities. There may be an impact on gene transcription from protein kinase A (PKA) as well as its downstream effectors, such as cAMP response element-binding protein (CREB). The position of CREB downstream of numerous growth signaling pathways implies its oncogenic potential in tumor cells. Tumor growth is associated with increased CREB expression and activation. PKA can be used as both an onco-drug target and a biomarker to find, identify, and stage tumors. Exploring cAMP effectors and their downstream pathways in cancer has become easier using exchange protein directly activated by cAMP (EPAC) modulators. This signaling system may inhibit or accelerate tumor growth depending on the tumor and its environment. As cAMP and its effectors are critical for cancer development, targeting them may be a useful cancer treatment strategy. Moreover, by reviewing the material from a distinct viewpoint, this review aims to give a knowledge of the impact of the cAMP signaling pathway and the related effectors on cancer incidence and development. These innovative insights seek to encourage the development of novel treatment techniques and new approaches.
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Proteínas Quinases Dependentes de AMP Cíclico , Neoplasias , Proteína de Ligação a CREB/metabolismo , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Transdução de SinaisRESUMO
Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management.
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PURPOSE: A metabolic abnormality such as obesity is a major obstacle in the maintenance of the human health system and causes various chronic diseases including type 2 diabetes, hypertension, cardiovascular diseases, as well as various cancers. This study was designed to summarize the recent scientific knowledge regarding the anti-obesity role of curcumin (diferuloylmethane), which is isolated from the herb curcuma longa, known to possess anti-inflammatory activities. However, little is known about its exact underlying molecular mechanisms in the treatment of obesity and metabolic diseases. Furthermore, cell cultures, animal models of obesity, and few human clinical and epidemiological studies have added the promise for future therapeutic interventions of this dietary compound. METHODS: An electronic search was performed using Science finder, Medline, Scopus, Google scholar and collected English language articles from 2000 to 2010, relating to the role of curcumin in obesity and metabolic diseases. RESULTS: Obesity has been classified as a growing epidemic and its associated metabolic disorders are considered a major risk to the health system. Curcumin interacts with specific proteins in adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells, where it suppresses several cellular proteins such as transcription factor NF-kB, STAT-3, Wnt/ß-catenin and activates PPAR-γ, Nrf2 cell signaling pathway. In addition, curcumin downregulates the inflammatory cytokines, resistin and leptin, and upregulates adiponectin as well as other associated proteins. The interactions of curcumin with several signal transduction pathways reverse insulin resistance, hyperglycemia, hyperlipidemia, and other inflammatory symptoms associated with obesity and metabolic diseases. CONCLUSION: The modulation of several cellular transduction pathways by curcumin has recently been extended to elucidate the molecular basis for obesity and obesity-related metabolic diseases. These findings might enable novel phytochemical treatment strategies as well as curcumin translation to the clinical practice for the treatment and prevention of obesity-related chronic diseases. Furthermore, the relatively low cost of curcumin, safety and proven efficacy make it advisable to include curcumin as part of healthy diet.
Assuntos
Anti-Inflamatórios/farmacologia , Curcumina/farmacologia , Doenças Metabólicas/tratamento farmacológico , Obesidade/tratamento farmacológico , Fitoterapia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Curcuma/química , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Doenças Metabólicas/epidemiologia , Obesidade/epidemiologia , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Although there have been many genome-wide association studies (GWAS) and selective sweep analyses to understand pig genomic regions related to growth performance, these methods considered only the gene effect and selection signal, respectively. In this study, we suggest the cross-population phenotype associated variant (XP-PAV) analysis as a novel method to determine the genomic variants with different effects between the two populations. XP-PAV analysis could reveal the differential genetic variants between the two populations by considering the gene effect and selection signal simultaneously. In this study, we used daily weight gain (DWG) and back fat thickness (BF) as phenotypes and the Landrace and Yorkshire populations were used for XP-PAV analysis. The main aim was to reveal the differential selection by considering the gene effect between Landrace and Yorkshire pigs. In the gene ontology analysis of XP-PAV results, differential selective genes in DWG analysis were involved in the regulation of interleukin-2 production and cell cycle G2/M transition. The protein modification and glycerophospholipid biosynthetic processes were the most enriched terms in the BF analysis. Therefore, we could identify genetic differences for immune and several metabolic pathways between Landrace and Yorkshire breeds using the XP-PAV analysis. In this study, we expect that XP-PAV analysis will play a role in determining useful selective variants with gene effects and provide a new interpretation of the genetic differences between the two populations.