Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet and genetics are among ...the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions, thereby disturbing body physiology. Specifically, the abundance of fibre‐metabolizing microbes is associated with weight loss and that of protein and fat‐metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thus influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes’ abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping GM, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be keys in the treatment of metabolic diseases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In recent years, a vast number of potential cancer therapeutic targets have emerged. However, developing efficient and effective drugs for the targets is of major concern. Hydrogen sulfide (H
S), one ...of the three known gasotransmitters, is involved in the regulation of various cellular activities such as autophagy, apoptosis, migration, and proliferation. Low production of H
S has been identified in numerous cancer types. Treating cancer cells with H
S donors is the common experimental technique used to improve H
S levels; however, the outcome depends on the concentration/dose, time, cell type, and sometimes the drug used. Both natural and synthesized donors are available for this purpose, although their effects vary independently ranging from strong cancer suppressors to promoters. Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with H
S donors which suggest their potential in cancer treatment. This review will analyze the potential of H
S donors in cancer therapy by summarizing key cellular processes and mechanisms involved.
Breast cancer is one of the most frequent cancers among women worldwide. Hyaluronic acid (HA) is one of the best biopolymers in terms of safety issues and has been widely used in drug delivery and ...tissue engineering. 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH) is a commonly used H2S donor. In this study, we designed and synthesized a conjugate, HA-ADT, by connecting HA with ADT-OH through chemical reactions. Our results indicated that HA-ADT could produce more H2S than NaHS and GYY4137. HA-ADT exerted more potent inhibitory effects than NaHS and GYY4137 in the proliferation, viability, migration, and invasion of human breast cancer cells. Similar trends were observed in the apoptosis and the protein levels of phospho (p)-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK, and p-ERK in human breast cancer cells. Furthermore, HA-ADT exhibited more powerful inhibitory effects on the growth of human breast cancer xenograft tumors in nude mice. In conclusion, HA-ADT could suppress the growth of human breast cancer cells through the inhibition of the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways. HA-ADT and its derivatives might be of great potential in the treatment of different types of cancer.
•HA-ADT produces more H2S than NaHS and GYY4137.•HA-ADT decreases the proliferation and viability of human breast cancer cells.•HA-ADT suppresses the migration and invasion of human breast cancer cells.•HA-ADT induces apoptosis through PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways.•HA-ADT inhibits the growth and angiogenesis of human breast cancer xenografts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Preoperative evaluation of the consistency of pituitary macroadenomas is important for neurosurgeons to prepare the surgical plan.
Purpose
To evaluate the diagnostic performance of texture ...analysis (TA) of diffusion‐weighted imaging (DWI) at a standard b‐value (b = 1000 s/mm2) and a high b‐value (b = 2000 s/mm2) for their ability to assess the tumor consistency of pituitary macroadenomas.
Study Type
Retrospective.
Population/Subjects
Fifty patients with histologically confirmed pituitary macroadenomas were classified as soft (n = 37) or hard (n = 13) types.
Field Strength/Sequence
Coronal T2‐weighted imaging (T2WI), Readout Segmentation of Long Variable Echo‐trains (RESOLVE) DWI at b = 1000 s/mm2 and b = 2000 s/mm2 were acquired with 3.0T MRI.
Assessment
The corresponding apparent diffusion coefficient (ADC) maps (ADC1000 and ADC2000) were registered to T2WI. Regions of interest (ROIs) were manually drawn along the solid part of the tumor from the coregistered T2WI‐ADC images. The texture parameters from T2WI, ADC1000, and ADC2000 were acquired.
Statistical Tests
The texture parameters were compared between the two types by using unpaired Student's t‐test. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to assess their diagnostic performance.
Results
Significant differences in TA parameters of ADC1000 and ADC2000 were observed between soft and hard types (P < 0.05 for all), whereas the TA of T2WI resulted in no significant difference (P > 0.05 for all). TA of ADC2000 provided a superior diagnostic performance compared with that of ADC1000 (P = 0.038). A combination of mean value and entropy of ADC2000 yielded an AUC, a sensitivity, and a specificity of 0.911, 78.4% and 92.3%, respectively.
Data Conclusion
TA of ADC values were useful for assessing the tumor consistency of pituitary macroadenomas. ADC2000 may facilitate better type discrimination.
Level of Evidence: 3
Technical Efficacy Stage: 2
J. Magn. Reson. Imaging 2020;51:1507–1513.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been recognized as a toxic gas and environment pollutant. However, increasing evidence suggests that H2S acts as a novel ...gasotransmitter and plays important roles in a variety of physiological and pathological processes in mammals. H2S is involved in many hepatic functions, including the regulation of oxidative stress, glucose and lipid metabolism, vasculature, mitochondrial function, differentiation, and circadian rhythm. In addition, H2S contributes to the pathogenesis and treatment of a number of liver diseases, such as hepatic fibrosis, liver cirrhosis, liver cancer, hepatic ischemia/reperfusion injury, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, hepatotoxicity, and acute liver failure. In this review, the biosynthesis and metabolism of H2S in the liver are summarized and the role and mechanism of H2S in liver health and disease are further discussed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal‐transducing agent providing unique features to its substrate nuclear proteins ...(PEST‐NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST‐NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST‐NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene‐based therapeutics are getting the attention of researchers because of their cell specificity. PEST‐NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST‐NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST‐NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST‐NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST‐mediated PTMs on activation, localization, stability, and protein–protein interactions of PEST‐NPs. We also recommend researchers to adopt a pragmatic approach in gene‐based cancer therapy.
1.PEST (proline, glutamic acid, serine, and threonine) motif is responsible for particular posttranslational modifications (PTMs) in their substrate nuclear proteins.
2.Insights into PTMs of nuclear proteins demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors.
3.PEST sequence enriched nuclear proteins (PEST‐NPs) are multivariate in their behavior.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumour necrosis factor‐α‐induced protein 8‐like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. ...Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non‐tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down‐regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down‐regulating the expression levels of Wnt3a, phospho (p)‐β‐Catenin, and p‐glycogen synthase kinase‐3β in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p‐Smad2, p‐Smad3, and transforming growth factor‐beta (TGF‐β) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/β‐Catenin and TGF‐β/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hydrogen sulfide (H
S) plays a key role in the regulation of physiological processes in mammals. The decline in H
S level has been reported in numerous renal disorders. In animal models of renal ...disorders, treatment with H
S donors could restore H
S levels and improve renal functions. H
S donors suppress renal dysfunction by regulating autophagy, apoptosis, oxidative stress, and inflammation through multiple signaling pathways, such as TRL4/NLRP3, AMP-activated protein kinase/mammalian target of rapamycin, transforming growth factor-β1/Smad3, extracellular signal-regulated protein kinases 1/2, mitogen-activated protein kinase, and nuclear factor kappa B. In this review, we summarize recent developments in the effects of H
S donors on the treatment of common renal diseases, including acute/chronic kidney disease, renal fibrosis, unilateral ureteral obstruction, glomerulosclerosis, diabetic nephropathy, hyperhomocysteinemia, drug-induced nephrotoxicity, metal-induced nephrotoxicity, and urolithiasis. Novel H
S donors can be designed and applied in the treatment of common renal diseases.
To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases.
Pathologically ...confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model.
The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts.
This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.
This study aims to investigate the value of radiomics parameters derived from contrast enhanced (CE) MRI in differentiation of hypovascular non-functional pancreatic neuroendocrine tumors ...(hypo-NF-pNETs) and solid pseudopapillary neoplasms of the pancreas (SPNs).
Fifty-seven SPN patients and twenty-two hypo-NF-pNET patients were enrolled. Radiomics features were extracted from T1WI, arterial, portal and delayed phase of MR images. The enrolled patients were divided into training cohort and validation cohort with the 7:3 ratio. We built four radiomics signatures for the four phases respectively and ROC analysis were used to select the best phase to discriminate SPNs from hypo-NF-pNETs. The chosen radiomics signature and clinical independent risk factors were integrated to construct a clinic-radiomics nomogram.
SPNs occurred in younger age groups than hypo-NF-pNETs (P < 0.0001) and showed a clear preponderance in females (P = 0.0185). Age was a significant independent factor for the differentiation of SPNs and hypo-NF-pNETs revealed by logistic regression analysis. With AUC values above 0.900 in both training and validation cohort (0.978 95% CI, 0.942-1.000 in the training set, 0.907 95% CI, 0.765-1.000 in the validation set), the radiomics signature of the arterial phase was picked to build a clinic-radiomics nomogram. The nomogram, composed by age and radiomics signature of the arterial phase, showed sufficient performance for discriminating SPNs and hypo-NF-pNETs with AUC values of 0.965 (95% CI, 0.923-1.000) and 0.920 (95% CI, 0.796-1.000) in the training and validation cohorts, respectively. Delong Test did not demonstrate statistical significance between the AUC of the clinic-radiomics nomogram and radiomics signature of arterial phase.
CE-MRI-based radiomics approach demonstrated great potential in the differentiation of hypo-NF-pNETs and SPNs.
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