Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.
Nonpolymer,
pH-sensitive carbon dots (pSCDs) were developed to overcome the disadvantages
of pH-sensitive polymers such as inevitable synthesis, wide distribution
of molecular weight, uncontrolled loading and release rate of drugs,
and toxicity by biodegradation. The pSCDs were synthesized via one
spot synthesis for 3 min using citric acid (CA) and 1-(3-aminopropyl)
imidazole (API). Imidazole groups were present on pSCD surfaces and
facilitated DOX loading via hydrophobic interactions (loading efficiency:
78.55%). The DOX-loaded pSCDs collapsed at tumoral pH (pH ∼
6.5) due to protonation of the imidazole groups, and DOX was released
about 7 times higher than the control group. The therapeutic effect
was confirmed in vitro using HCT-116 (human colon cancer), PANC-1
(human pancreatic cancer), and SKBR-3 (human breast cancer) cells.
Additionally, the DOX-loaded pSCDs successfully inhibited tumor growth
in an HCT-116-bearing mouse model and did not show toxicity. These
results indicate that a nonpolymeric pSCDs platform has the potential
to be used as a cancer targeting therapeutic material.
In the past decade, immunotherapies have been emerging as an effective way to treat cancer. Among several categories of immunotherapies, immune checkpoint inhibitors (ICIs) are the most well-known and widely used options for cancer treatment. Although several studies continue, this treatment option has yet to be developed into a precise application in the clinical setting. Recently, omics as a high-throughput technique for understanding the genome, transcriptome, proteome, and metabolome has revolutionized medical research and led to integrative interpretation to advance our understanding of biological systems. Advanced omics techniques, such as multi-omics, single-cell omics, and typical omics approaches, have been adopted to investigate various cancer immunotherapies. In this review, we highlight metabolomic studies regarding the development of ICIs involved in the discovery of targets or mechanisms of action and assessment of clinical outcomes, including drug response and resistance and propose biomarkers. Furthermore, we also discuss the genomics, proteomics, and advanced omics studies providing insights and comprehensive or novel approaches for ICI development. The overview of ICI studies suggests potential strategies for the development of other cancer immunotherapies using omics techniques in future studies.
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