Recent preclinical/clinical studies have underscored the significant impact of tumor microenvironment (TME) on tumor progression in diverse scenarios. Highly heterogeneous and complex, the tumor microenvironment is composed of malignant cancer cells and non-malignant cells including endothelial cells, fibroblasts, and diverse immune cells. Since immune compartments play pivotal roles in regulating tumor progression via various mechanisms, understanding of their multifaceted functions is crucial to developing effective cancer therapies. While roles of lymphoid cells in tumors have been systematically studied for a long time, the complex functions of myeloid cells have been relatively underexplored. However, constant findings on tumor-associated myeloid cells are drawing attention, highlighting the primary effects of innate immune cells such as monocytes and neutrophils in disease progression. This review focuses on hitherto identified contextual developments and functions of monocytes and neutrophils with a special interest in solid tumors. Moreover, ongoing clinical applications are discussed at the end of the review.

There exists evidence for the presence of ultrashort loop feedback circuits of gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. It is, however, uncertain whether a similar mechanism is involved in the regulation of GnRH gene expression in vivo. Furthermore, little is known about the regulation of GnRH receptor (GnRHR) expression in the brain. In the present study, we examined the regulation of GnRH and its receptor gene expression by GnRH in vivo. A GnRH agonist, [D-Ala6, des-Gly10]GnRH-ethylamide (des-Gly GnRH), was administered by intracerebroventricular (i.c.v.) injection via the lateral ventricle of ovariectomized and estradiol (OVX + E)-treated rats. The amounts of GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain slices by respective competitive reverse transcription-polymerase chain reactions. The i.c.v. administration of des-Gly GnRH significantly decreased GnRH and GnRHR mRNA expression in a dose-and time-related manner: des-Gly GnRH (6 ng) suppressed GnRH and GnRHR mRNA expression within 2 h, and the suppression was maintained without significant variation until 8 h after treatment. Treatment with Antide, [N-Ac-D-Nal(2)1, pCl-D-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6, Lys(iPR)8, D-Ala10]GnRH (10 ng), a potent GnRH antagonist, did not alter GnRH mRNA expression, but prevented des-Gly GnRH-induced suppression of GnRH mRNA expression. Antide alone decreased GnRHR mRNA expression, but failed to alter agonist-induced suppression of GnRHR mRNA expression. These results demonstrate the existence of an ultrashort loop feedback mechanism for GnRH gene expression in the POA, along with homologous down-regulation of GnRHR mRNA expression in the pMBH.

Background Although many therapeutic agents have been developed, only a few drugs are known to target multiple pathogenic factors in the treatment of acne. Objective The purpose of this study was to identify a new drug candidate, platycodin D, which is a substance extracted from the root of Platycodon grandiflorum . Methods Using western blotting and Cell Counting Kit-8 assay, we studied the effects of platycodin D on SEB-1 sebocytes, fibroblasts, and keratinocytes. We investigated its effects in view of lipogenesis, collagen production, anti-inflammatory activity, and dyskeratinization. Results In SEB-1 sebocytes, platycodin D showed a sebosuppressive effect by downregulating ERK and insulin- like growth factor-1R/PI3K/Akt/sterol-regulatory element binding protein-1 signaling pathways. In addition, adiponectin, one of the adipokines responsible for sebum production, was decreased in platycodin D-treated SEB-1 sebocytes. In fibroblasts, platycodin D increased collagen production and reduced inflammation by inhibiting nuclear factor kappa B and matrix metalloproteinases. Platycodin D also showed anti-inflammatory effects on keratinocytes. It also suppressed keratin 16 expression induced by lipopolysaccharide. Furthermore, platycodin D showed no cytotoxicity on both SEB-1 sebocytes and fibroblasts. Conclusion Our data demonstrate the clinical feasibility of platycodin D for acne treatment and the prevention of acne scarring by sebosuppressive and anti-inflammatory effects, as well as through an increase in collagen levels.

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Background: Diabetes damages the collagen in the skin. No study has investigated the relationship between the treatment initiation time and the degree of collagen recovery. This study aimed to evaluate the effects of the initiation time of glycemic control on collagen recovery and to determine the basic molecules mediating the process. Methods: Streptozotocin-induced diabetic rats were divided into five groups: normal controls (C), those with untreated diabetes (DM), and those with diabetes treated with daily insulin injections from 7 weeks (7W), 10 weeks (10W), and 13 weeks (13W) after diabetes induction. The levels of collagen and several molecules were compared among skin tissues collected at 14 weeks. Results: The amounts of total collagen, collagen 1, and collagen 3 were significantly lower in DM than in C. Among the treated groups, recovery reaching normal levels was only observed in 7W and 10W. The earlier the treatment began, the greater was the collagen recovery. Similar to that of collagen, the expression of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 receptor (IGF-1R) significantly decreased in DM compared with that in C. Higher recovery of TGF-β1 and VEGF was detected in groups with earlier treatment, whereas the IGF-1R level was identically elevated in all treated groups. The results suggest that these molecules affect collagen recovery at different time points during glycemic control. Conclusion: The initiation time of glycemic control is expected to have a considerable effect on collagen recovery in the diabetic skin through modulation of TGF-β1, VEGF, and IGF-1R.