Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking.We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

Diabetic wound (DW) is one of the leading complications of patients having a long history of uncontrolled diabetes. Moreover, it also imposes an economic burden on people suffering from wounds to manage the treatment. The major impending factors in the treatment of DW are infection, prolonged inflammation and decreased oxygen levels. Since these non-healing wounds are associated with an extended recovery period, the existing therapies provide treatment for a limited period only. The areas covered in this review are general sequential events of wound healing along with DW’s pathophysiology, the origin of DW and success, as well as limitations of existing therapies. This systematic review’s significant aspect is to highlight the fabrication, characterization and applications of various acellular scaffolds used to heal DW. In addition to that, cellular scaffolds are also described to a limited extent.

Diabetic wound (DW) is one of the leading complications of patients having a long history of uncontrolled diabetes. Moreover, it also imposes an economic burden on people suffering from wounds to manage the treatment. The major impending factors in the treatment of DW are infection, prolonged inflammation and decreased oxygen levels. Since these non-healing wounds are associated with an extended recovery period, the existing therapies provide treatment for a limited period only. The areas covered in this review are general sequential events of wound healing along with DW’s pathophysiology, the origin of DW and success, as well as limitations of existing therapies. This systematic review’s significant aspect is to highlight the fabrication, characterization and applications of various acellular scaffolds used to heal DW. In addition to that, cellular scaffolds are also described to a limited extent.

BACKGROUND/AIMS: The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis. METHODS: Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks. RESULTS: The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture. CONCLUSIONS: Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.
Arousal ; Cytidine Triphosphate ; Extremities ; Fibrosis ; Humans ; Sleep Initiation and Maintenance Disorders

Segmentation of fundamental heart sounds–S1 and S2 is important for automated monitoring of cardiac activity including diagnosis of the heart diseases. This pa-per proposes a novel hybrid method for S1 and S2 heart sound segmentation using group sparsity denoising and variation mode decomposition (VMD) technique. In the proposed method, the measured phonocardiogram (PCG) signals are denoised using group sparsity algorithm by exploiting the group sparse (GS) property of PCG signals. The denoised GS-PCG signals are then decomposed into subsequent modes with specific spectral characteristics using VMD algorithm. The appropriate mode for further processing is selected based on mode central frequencies and mode energy. It is then followed by the extraction of Hilbert envelope (HEnv) and a thresholding on the selected mode to segment S1 and S2 heart sounds. The performance advantage of the proposed method is verified using PCG signals from benchmark databases namely eGeneralMedical, Littmann, Washington, and Michigan. The proposed hybrid algorithm has achieved a sensitivity of 100%, positive predictivity of 98%, accuracy of 98% and detection error rate of 1.5%. The promising results obtained suggest that proposed approach can be considered for automated heart sound segmentation.
Benchmarking ; Diagnosis ; Heart Diseases ; Heart Sounds ; Heart ; Methods ; Michigan ; Washington