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Topic Review
Cellular Components of Tumor Microenvironment  in cHL
Classic Hodgkin lymphoma (cHL) is a lymphoid neoplasm composed of rare neoplastic Hodgkin and Reed–Sternberg (HRS) cells surrounded by a reactive tumor microenvironment (TME) with suppressive properties against anti-tumor immunity. TME is mainly composed of T cells (CD4 helper, CD8 cytotoxic and regulatory) and tumor-associated macrophages (TAMs), but the impact of these cells on the natural course of the disease is not absolutely understood. 
  • 414
  • 28 Jun 2023
Topic Review
Atoh8 in Disease
Atoh8 is a transcription factor that belongs to a large superfamily of transcriptional regulators called bHLH proteins. In spite of two decades of research, multiple questions regarding its molecular function and involved mechanisms remain elusive.
  • 413
  • 29 Jan 2022
Topic Review
CaFtsH06
we examined the transcriptional regulation of the CaFtsH06 gene in the R9 thermo-tolerant pepper (Capsicum annuum L.) line. The results of qRT-PCR revealed that CaFtsH06 expression was rapidly induced by abiotic stress treatments, including heat, salt, and drought. The CaFtsH06 protein was localized to the mitochondria and cell membrane. Additionally, silencing CaFtsH06 increased the accumulation of malonaldehyde content, conductivity, hydrogen peroxide (H2O2) content, and the activity levels of superoxide dismutase and superoxide (·O2−), while total chlorophyll content decreased under these abiotic stresses. Furthermore, CaFtsH06 ectopic expression enhanced tolerance to heat, salt, and drought stresses, thus decreasing malondialdehyde, proline, H2O2, and ·O2− contents while superoxide dismutase activity and total chlorophyll content were increased in transgenic Arabidopsis. Similarly, the expression levels of other defense-related genes were much higher in the transgenic ectopic expression lines than WT plants. These results suggest that CaFtsH06 confers abiotic stress tolerance in peppers by interfering with the physiological indices through reducing the accumulation of reactive oxygen species, inducing the activities of stress-related enzymes and regulating the transcription of defense-related genes, among other mechanisms. The results of this study suggest that CaFtsH06 plays a very crucial role in the defense mechanisms of pepper plants to unfavorable environmental conditions and its regulatory network with other CaFtsH genes should be examined across variable environments
  • 412
  • 12 Jul 2021
Topic Review
Redox Chemistry and Ubiquitylation
The ubiquitin-proteasome system (UPS) is a highly regulated mechanism for protein degradation that regulates many biological processes to maintain cellular homeostasis. A protein is targeted for degradation upon ubiquitylation, where the small 8.6 kDa protein, ubiquitin, is covalently attached to the target protein through an isopeptide bond. Ubiquitylation involves the sequential transfer of ubiquitin through a three-enzyme cascade—an ubiquitin-activating enzyme (E1), an ubiquitin-conjugating enzyme (E2), and an ubiquitin ligase (E3).
  • 412
  • 30 Aug 2021
Topic Review
Circadian Regulation of Retinal Pigment Epithelium Function
The retinal pigment epithelium (RPE) is a single layer of cells located between the choriocapillaris vessels and the light-sensitive photoreceptors in the outer retina. The RPE performs physiological processes necessary for the maintenance and support of photoreceptors and visual function. Among the many functions performed by the RPE, the timing of the peak in phagocytic activity by the RPE of the photoreceptor outer segments that occurs 1–2 h. after the onset of light has captured the interest of many investigators and has thus been intensively studied. Several studies have shown that this burst in phagocytic activity by the RPE is under circadian control and is present in nocturnal and diurnal species and rod and cone photoreceptors. Previous investigations have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. However, the anatomical location of the circadian controlling this activity is not clear. Experimental evidence indicates that the circadian clock, melatonin, dopamine, and integrin signaling play a key role in controlling this rhythm.
  • 412
  • 21 Mar 2022
Topic Review
Synthetic Vulnerabilities in the KRAS Pathway
Mutations in Kristen Rat Sarcoma viral oncogene (KRAS) are among the most frequent gain-of-function genetic alterations in human cancer. Most KRAS-driven cancers depend on its sustained expression and signaling. Despite spectacular recent success in the development of inhibitors targeting specific KRAS alleles, the discovery and utilization of effective directed therapies for KRAS-mutant cancers remains a major unmet need.
  • 412
  • 24 Jun 2022
Topic Review
Gq Signaling in Autophagy Control
All processes in human physiology relies on homeostatic mechanisms which require the activation of specific control circuits to adapt the changes imposed by external stimuli. One of the critical modulators of homeostatic balance is autophagy, a catabolic process that is responsible of the destruction of long-lived proteins and organelles through a lysosome degradative pathway. Identification of the mechanism underlying autophagic flux is considered of great importance as both protective and detrimental functions are linked with deregulated autophagy. At the mechanistic and regulatory levels, autophagy is activated in response to diverse stress conditions (food deprivation, hyperthermia and hypoxia), even a novel perspective highlight the potential role of physical forces in autophagy modulation. To understand the crosstalk between all these controlling mechanisms could give people new clues about the specific contribution of autophagy in a wide range of diseases including vascular disorders, inflammation and cancer.
  • 412
  • 02 Sep 2022
Topic Review
Cellular Senescence in Metabolic-Associated Kidney Disease
Metabolic syndrome (MetS), a complex of interrelated risk factors for cardiovascular disease and diabetes, is characterized by central obesity (increased waist circumference), hyperglycemia, dyslipidemia (high triglyceride blood levels and low high-density lipoprotein blood levels), and increased blood pressure. As an important metabolic organ, the kidney has a close relationship with metabolic syndrome. MetS usually aggravates kidney damage and causes or aggravates kidney pathologies, typically manifested as microalbuminuria and renal insufficiency. For example, severe obesity can lead to glomerular hypertrophy and glomerular sclerosis, leading to proteinuria. This is called obesity-related nephropathy, which was first discovered in 1974 by Weisinger. Diabetic capillary complications can lead to pathological changes to the kidney, thickening of the glomerular capillary basement membrane, and widening of the mesangium. Clinical manifestations can change from proteinuria to uremia. Similarly, hypertension-related nephropathy is a serious complication of hypertension, which is characterized by arteriosclerotic kidneys. Clinical manifestations include nocturia increasing, albuminuria, and finally, uremia. For hyperlipidemia, although there is no hyperlipidemia-related nephropathy, a large number of studies have shown that lipids have an effect on the proliferation and signal transduction of glomerular cells, and accelerate glomerulosclerosis through inflammatory reaction. These metabolic diseases often exist at the same time, and can promote each other; furthermore, they share a common pathophysiological basis: insulin resistance. It is widely believed that there exists a significant relationship between hyperglycemia, hypertension, and hyperlipemia.
  • 415
  • 18 Nov 2022
Topic Review
Pyrvinium Pamoate Mechanisms of Action as an Anti-Cancer Agent
Pyrvinium, a lipophilic cation belonging to the cyanine dye family, has been used in the clinic as a safe and effective anthelminthic for over 70 years. Its structure, similar to some polyaminopyrimidines and mitochondrial-targeting peptoids, has been linked with mitochondrial localization and targeting. Unsurprisingly for a small-molecule compound, pyrvinium pamoate (PP) has been shown to act through multiple mechanisms. The majority of the published articles assessing PP specifically as an anticancer therapeutic have focused on two main MOA, which appear to be at the root of PP action: inhibition of the WNT pathway and inhibition of mitochondrial function.
  • 412
  • 30 Dec 2022
Topic Review
P27Kip1
The Cyclin-dependent kinase (CDK) regulator p27Kip1 is a gatekeeper of G1/S transition. It also regulates G2/M progression and cytokinesis completion, via CDK-dependent or -independent mechanisms. Recently, other important p27Kip1 functions have been described, including the regulation of cell motility and migration, the control of cell differentiation program and the activation of apoptosis/autophagy.
  • 411
  • 13 Sep 2021
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