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Sepsis is a systemic inflammatory syndrome that results in multiple-organ failure caused by a dysregulated host immune response to microbial infection. Astragali complanati semen extract (ACSE) exhibits pharmacological activities, including antioxidant, anticancer, antiaging, and anti-diabetes effects. It is widely used in traditional medicine to treat liver and kidney diseases; however, the protective effect of ACSE on sepsis and its mechanisms are unknown. In the present study, we investigated the anti-inflammatory effects and potential mechanisms of the action of ACSE on sepsis. We show that ACSE improved survival rates in mouse models of acute sepsis induced by CLP (cecal ligation and puncture) and LPS stimulation. ACSE administration decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in sepsis-induced mice. Furthermore, ACSE reduced the levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of septic mice. ACSE treatment inhibited the expression of these proinflammatory genes in LPS-stimulated J774 macrophages. Moreover, ACSE inhibited the phosphorylation of the IκB kinase (IKK) and the nuclear translocation of p65 NF-κB by LPS stimulation in macrophages. These results reveal the mechanism underlying the protective effect of ACSE against sepsis by inhibiting NF-κB activation and suggest that ACSE could be a potential therapeutic candidate to treat acute inflammatory diseases.
Asunto(s)
Planta del Astrágalo , Sepsis , Choque Séptico , Animales , Ratones , Lipopolisacáridos/toxicidad , FN-kappa B , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Etanol , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.
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Neoplasias , Plantas Medicinales , Humanos , Pronóstico , Caquexia/etiología , Caquexia/genética , Simulación del Acoplamiento Molecular , Farmacología en Red , Perfilación de la Expresión Génica , Extractos Vegetales , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
Textile wastewater accounts for a significant proportion of industrial wastewater worldwide. In particular, dye wastewater accounts for a large proportion and consists of non-degradable dyes, which are substances resistant to biodegradation. Methylene blue is a representative example of such non-degradable dyes. It is not biologically degraded and exhibits toxicity. Various methods for their decomposition are currently being studied. Advanced oxidation processes (AOPs), which generate highly reactive hydroxyl radicals that oxidize and degrade pollutants, have been actively studied. Particularly, the photocatalytic degradation method using TiO2 nanoparticles is one of the most actively studied fields; however, there are still concerns regarding the toxicity of nanoparticles. Research is currently being conducted on AOPs using the cavitation phenomenon of ultrasonic waves. However, achieving high efficiency using existing ultrasonic equipment is difficult. Therefore, in this study, we evaluated a new water treatment technology through AOPs using a focused ultrasonic system with a cylindrical piezoelectric ceramic structure. After determining the optimal conditions for degradation, the degradation process was evaluated as a useful tool for mitigating the toxicity of methylene blue. We found that, under the optimal conditions of 100 W intensity at a frequency of 400 kHz, this system is a helpful instrument for degradation and a new water treatment technology suitable for removing ecotoxicity and genotoxicity.
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Population aging has increased the global prevalence of aging-related diseases, including cancer, sarcopenia, neurological disease, arthritis, and heart disease. Understanding aging, a fundamental biological process, has led to breakthroughs in several fields. Cellular senescence, evinced by flattened cell bodies, vacuole formation, and cytoplasmic granules, ubiquitously plays crucial roles in tissue remodeling, embryogenesis, and wound repair as well as in cancer therapy and aging. The lack of universal biomarkers for detecting and quantifying senescent cells, in vitro and in vivo, constitutes a major limitation. The applications and limitations of major senescence biomarkers, including senescence-associated ß-galactosidase staining, telomere shortening, cell-cycle arrest, DNA methylation, and senescence-associated secreted phenotypes are discussed. Furthermore, explore senotherapeutic approaches for aging-associated diseases and cancer. In addition to the conventional biomarkers, this review highlighted the in vitro, in vivo, and disease models used for aging studies. Further, technologies from the current decade including multi-omics and computational methods used in the fields of senescence and aging are also discussed in this review. Understanding aging-associated biological processes by using cellular senescence biomarkers can enable therapeutic innovation and interventions to improve the quality of life of older adults.
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Adipogenesis is a process that differentiates new adipocytes from precursor cells and is tightly regulated by several factors, including many transcription factors and various post-translational modifications. Recently, new roles of adipogenesis have been suggested in various diseases. However, the molecular mechanisms and functional modulation of these adipogenic genes remain poorly understood. This review summarizes the regulatory factors and modulators of adipogenesis and discusses future research directions to identify novel mechanisms regulating adipogenesis and the effects of adipogenic regulators in pathological conditions. The master adipogenic transcriptional factors PPARγ and C/EBPα were identified along with other crucial regulatory factors such as SREBP, Kroxs, STAT5, Wnt, FOXO1, SWI/SNF, KLFs, and PARPs. These transcriptional factors regulate adipogenesis through specific mechanisms, depending on the adipogenic stage. However, further studies related to the in vivo role of newly discovered adipogenic regulators and their function in various diseases are needed to develop new potent therapeutic strategies for metabolic diseases and cancer.
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Adipocitos , Adipogénesis , Adipogénesis/fisiología , Humanos , Animales , Adipocitos/metabolismo , PPAR gamma/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión GénicaRESUMEN
The growing interest in microalgae and cyanobacteria biomass as an alternative to traditional animal feed is hindered by high production costs. Using wastewater (WW) as a cultivation medium could offer a solution, but this approach risks introducing harmful substances into the biomass, leading to significant safety concerns. In this study, we addressed these challenges by selectively extracting nitrates and phosphates from WW using drinking water treatment residuals (DWTR) and chitosan. This method achieved peak adsorption capacities of 4.4 mg/g for nitrate and 6.1 mg/g for phosphate with a 2.5 wt% chitosan blend combined with DWTR-nitrogen. Subsequently, these extracted nutrients were employed to cultivate Spirulina platensis, yielding a biomass productivity rate of 0.15 g/L/d, which is comparable to rates achieved with commercial nutrients. By substituting commercial nutrients with nitrate and phosphate from WW, we can achieve a 18 % reduction in the culture medium cost. While the cultivated biomass was initially nitrogen-deficient due to low nitrate levels, it proved to be protein-rich, accounting for 50 % of its dry weight, and contained a high concentration of free amino acids (1260 mg/g), encompassing all essential amino acids. Both in vitro and in vivo toxicity tests affirmed the biomass's safety for use as an animal feed component. Future research should aim to enhance the economic feasibility of this alternative feed source by developing efficient adsorbents, utilizing cost-effective reagents, and implementing nutrient reuse strategies in spent mediums.