Publications

The 2021 online editorial board meeting of the <i>World Journal of Diabetes</i> (<i>WJD</i>) was held on November 9, 2021. Jin-Lei Wang, General Manager on behalf of the Baishideng Publishing Group, and Professor Islam, one of the Editors-in-Chiefs (EiCs) of the <i>WJD</i>, organized the meeting. Three EiCs and 18 Baishideng Publishing Group staff attended the meeting. The meeting goal was to brief the EiCs on the journal's performance, discuss the issues of concern of the EiCs, and gather ideas for the journal's development in 2022. As of November 8, the <i>WJD</i> had received 287 manuscripts since the year's start, among which 122 met the criteria for publication. These numbers represent an increase of 117.4% for submissions and 110.3% for publications compared to those in 2020. However, how to effectively control the academic quality of manuscripts and attract high-quality original article submissions remain a challenge. The EiCs provided feedback and suggestions centered on three topics: (1) Who should and how to control the academic quality of the manuscripts; (2) How the EiCs perform their responsibilities; and (3) The distinctive and shared responsibilities of the publisher and the EiCs.

The outbreak of coronavirus disease (COVID-19) caused by a novel RNA virus emerged at the end of 2019. Most of the patient's symptoms are mild to moderate, and influenza, acute respiratory distress syndrome (ARDS) and multi-organ failure are common. The disease is mild to moderate in most patients and is reported in many cases such as pneumonia, ARDS and multi-organ dysfunction. This study's objective is to evaluate 25 natural compounds from Citrus limon (CL) used by comprehensive molecular docking, density functional theory (DFT) and molecular dynamics analysis against SARS-CoV-2 main protease (M^pro). Among all the experimental compounds, diosmetin has shown the best docking values against the M^pro of SARS-CoV-2 compared to the standard antiviral drug. In DFT calculations, the order associated with biochemical reactivity is as follows: eriodictoyl > quercetin > spinacetin > diosmetin > luteolin > apigenin, whereas the regions of oxygen and hydrogen atoms from the selected isolated compounds are appropriate for electrophilic and nucleophilic attacks, respectively. Also, HOMO-LUMO and global descriptors values indicated a promising result of these compounds. Moreover, a molecular dynamics simulation study revealed the stable conformation and binding pattern in a stimulating environment of natural compounds CL. Considering molecular docking, simulation, and DFT analysis of the selected compounds, notably eriodictoyl, quercetin, and diosmetin showed good potential against SARS-CoV-2 M^pro. Our in silico study revealed promising antiviral activity, which may be considered a potential key factor or a therapeutic target for COVID-19.Communicated by Ramaswamy H. Sarma.

Energy (ATP) is essentially required to keep activity of our body, for example, the brain consumes a lot of ATP required for the Na+,K+-ATPase (pump) to maintain the low intracellular Na+ concentration essentially important for generation of the action potential for keeping neuronal activity. Under the normal condition, protons (H+) are produced as by-products of ATP generation. Various types of proton-excluding transporters exclude the produced protons to the interstitial fluid to keep the normal intracellular pH (Figure 1). The excluded protons move into the blood vessel via the interstitial space (Figure 1). Under the normal condition, the pH of arterial blood and interstitial fluid is not changed mainly via excretion of the produced protons into urine and partly via the lung as CO2 (Figure 1). Even if protons are transported into blood vessels, the pH of arterial blood is strictly controlled within the range of 7.35–7.45 by strong pH buffering factors such as hemoglobin (Hb) and albumin (Figure 2) (Aoi, Zou, Xiao, & Marunaka, 2020; Marunaka, 2018). In contrast, the interstitial fluid has only relatively weak pH buffers such bicarbonate and phosphate (Figure 2), therefore the interstitial fluid pH is variable depending on the metabolic condition (i.e., the amounts of produced protons) (Figure 2). Compared with normal conditions, much more protons are produced via glycolysis in cancer (Warburg effect) and diabetes (Figure 3A) (Bhattacharya, Omar, Feroz, & Soong, 2016; Chen, Liu, Li, & Chen, 2018; Gillies, Pilot, Marunaka, & Fais, 2019; Liberti & Locasale, 2016; Lu, 2019; Pillai et al., 2019; Potter, Newport, & Morten, 2016). The large amount of produced protons are excluded to the interstitial fluid to keep the normal intracellular pH by highly expressed acid transporters such as monocarboxylate transporter, H+-ATPase (pump), and Na+/H+ exchanger (Figure 1): most parts of the protons move into blood vessels, but some parts of the protons remain in the interstitial fluid (Figure 3A). Even in the case that a large amount of protons move into blood vessels, the pH of arterial blood is strictly controlled within the range of 7.35–7.45 by strong pH buffering factors such as hemoglobin (Hb) and albumin (Figure 2) (Aoi et al., 2020; Marunaka, 2018). In contrast, the local acidity around cells (interstitial fluids) less than pH of 7.0 (in some case, pH becomes ∼6.2; Puppulin et al., 2018) occurs in cases of cancers and diabetes. The difference of pH control in body fluids depends on the presence of pH buffer factors, since the interstitial fluid has no strong pH buffers such as Hb and albumin (Figure 2) (Aoi et al., 2020; Marunaka, 2018). The absence of strong pH buffers such as Hb and albumin in the interstitial fluid different from blood is a weak point regarding pH control. However, if the interstitial fluid would have strong pH buffers such as Hb and albumin, the collection of the metabolites produced in metabolic tissues into the capillary blood vessels driven by oncotic osmotic pressures does not function, resulting in death. This means that the absence of strong pH buffers in the interstitial fluid are essential events for maintenance of our life. Thus, occurrence of the local acidity around cells in diabetes and cancer is not avoided in usual cases. As mentioned above, cancer cells with no mitochondrial function express highly acid-excluding transporters, causing extremely high acidity in the interstitial fluid (Figure 3) (Gillies et al., 2019; Pillai et al., 2019; Puppulin et al., 2018). In contrast, normal cells express much less acid-excluding transporters compared with cancer cells (Gillies et al., 2019; Pillai et al., 2019): this means that normal cells has much weak ability defensing acidic environments, resulting in being easily destroyed by acidic environments. Thus, cancer cells destroy normal cells by acidifying the extracellular environments around normal cells, then produce the growing-up space for cancer cells themselves. The acidity would also diminish the activity and expression of cell adhesion factor, enabling for cancer cells to detach themselves from the primary lesion and cause metastases (Gillies et al., 2019; Pillai et al., 2019; Sumarokova et al., 2018). Some foods, so-called "alkalizing foods," have strong ability to elevate the lowered pH of body fluids observed in cancer and diabetes. The word of "alkalizing foods" is very popularly disseminated; however, the alkalizing mechanism is not so well understood. Representative "alkalizing foods" are weak organic acids containing carboxyl groups (the lower part of Figure 3B) (Aoi et al., 2020; Marunaka, 2018). Weak organic acids containing carboxyl groups are really acids at the oral intake (the lower part of Figure 3B), however only the carboxyl group but not the proton (H+) is absorbed via the intestine and the colon (the lower part of Figure 3B). The absorbed part of carboxyl group is an important factor chelating protons (H+) produced inside of the body (the upper part of Figure 3B). Acidity of the interstitial fluid around cells observed in diabetes (Aoi et al., 2013; Hosogi et al., 2018; Marunaka, Yoshimoto, Aoi, Hosogi, & Ikegaya, 2014) produces insulin resistance (Hayata, Miyazaki, Niisato, Yokoyama, & Marunaka, 2014). The improvement of acidity of the interstitial fluid (elevation of pH) increases insulin sensitivity (improvement of insulin resistance) (Aoi et al., 2013; Hosogi et al., 2018). Thus, the intake of alkalizing foods would elevate the lowed interstitial fluid pH in diabetes and cancer, resulting in improvement of insulin resistance and prevention of cancer cell growth and metastasis (Aoi et al., 2020; Marunaka, 2018). This work was supported by a grant-in-aid from Japan Society of the Promotion of Science (18H03182 to Y.M.).

This review highlights main bioactive compounds and important biological functions especially anticancer effects of the garlic. In addition, we review current literature on the stability and bioavailability of garlic components. Finally, this review aims to provide a potential strategy for using nanotechnology to increase the stability and solubility of garlic components, providing guidelines for the qualities of garlic products to improve their absorption and prevent their early degradation, and extend their circulation time in the body. The application of nanotechnology to improve the bioavailability and targeting of garlic compounds are expected to provide a theoretical basis for the functional components of garlic to treat human health. We review the improvement of bioavailability and bioactivity of garlic bioactive compounds via nanotechnology, which could promisingly overcome the limitations of conventional garlic products, and would be used to prevent and treat cancer and other diseases in the near future.

Abstract Recent studies have suggested that in addition to promoter region, DNA methylation in intragenic and intergenic regions also changes during physiological processes and disease. The current study showed that feeding of black raspberries (BRBs) to Apc Min mice suppressed colon and intestinal tumors. MBDCap‐seq suggested that dietary BRBs hypomethylated promoter, intragenic, and intergenic regions. Annotation of those regions highlighted genes in pathways involved in immune regulation, inflammatory signaling, production of nitric oxide and reactive oxygen species, and progression of colorectal cancer. BRB phytochemicals (e.g., ellagic acid, anthocyanins, oligosaccharides) and their gut bacterial metabolites (e.g., urolithin, protocatechuic acid, short‐chain fatty acids) inhibited DNMT1 and DNMT3B activities in a cell‐free assay. Our results suggest that BRBs’ hypomethylating activities result from the combined effects of multiple BRB phytochemicals and their gut bacterial metabolites. Because similar substances are found in many plant products, our results with BRBs might also apply to commonly consumed fruits and vegetables.

Moya, A1; Sineiro, E.1; Castiñeira, M. C.2; Gomara, S. M.1; Mojon, A.3; Fontao, M. J.3; Lorenzo, S.3; Ayala, D. E.3; Hermida, R. C.3 on behalf of Hygia Project Investigators Author Information