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Background: Science of medicine in the post-genomic era has significantly enhanced the knowledge of human diseases. These advancements could shed light to the translation of these benefits into drug therapeutics. Drug repurposing is a strategy that plays a pivotal role to provide novel insights into disease biology and further drive drug discovery as the ultimate goal. Herein, the current study aimed to analyse the global trends of drug repurposing peer-review publications from 2003 until 2022. Methods: We retrieved 1.371 articles related to drug repurposing studies and used similar terms and keywords, including “drug repositioning”, “drug repurposing”, “drug reprofiling”, “drug reusing”, and “drug recycling”. Results: The number of drug repurposing publications has increased dramatically from 2003 through 2022. Besides, the most active country in publishing drug repurposing research is the United States, followed by China, India, the United Kingdom, and Italy, respectively. Meanwhile, the top five frequently used keywords are drug repurposing (n = 336), drug repositioning (n = 335), COVID-19 (n = 134), SARS-CoV-2 (n = 135), and molecular docking (n = 67). Conclusions: This study emphasizes the importance of conducting active research collaboration in drug repurposing and drug repositioning especially pertaining to the COVID-19 pandemic.

Excessive alcohol consumption can lead to serious live injury. Alcohol is a source of free radicals that can cause oxidative stress. The provision of antioxidants can counter the effects of free radicals that enter the body. The skin of the Arabica coffee fruit contains antioxidant compounds that can be used as a hepatoprotective in the liver. The skin of the Arabica coffe fruit contains antioxidant compounds that may have a hepatoprotective effect on the liver. This study aimed to determine the effect of extract of arabica coffee fruit skin on necrosis, infiltration and haemorrhage in the liver tissue of 15% EtOH-induced mice for 15 days. The animals used for this study were eight weeks old male Balb/c strain mouse weighing approximately 30-40 grams. This research is an experimental study. There were five groups: the control group (K), the 15% ethanol treatment group (E), and the ethanol-induced group and given different doses of arabica coffee skin extract: 125 mg/kg BW. (A), 250 mg / kg BW (B) and 500 mg / kg BW (C). Observation and identification of necrosis, hepatocyte infiltration and haemorrhage were carried out by using Hematoxylin-eosin staining. The data analysis used was One way ANOVA and continued by Duncan Multiple Range Test (DMRT). The histopathological observations showed that the extract of arabica coffee fruit skin at a 250 mg/kg BW dose reduced the number of cell necrosis. There was no infiltration of inflammatory and hemorrhagic cells in the liver of 15% EtOH-induced mice. This study concludes that the extract of the skin of the Arabica coffee fruit has hepatoprotective potential in 15% EtOH-induced mice.

With the rapid development of cell-based therapy, the source of stem cells derived from non-invasive techniques have been intensively studied for their potential to replace the invasive source of stem cells. One of the alternative sources of stem cells is the cells taken from human breastmilk. Human breastmilk is always readily available, easy to access and can last for an extended period. Unfortunately, the standard protocol to isolate the cells from breastmilk is still not well explained. Our study aimed to investigate three main questions in human breastmilk stem cells: the optimal lactation stage, isolation and culture method, and the characterization of human breastmilk stem cells. We searched in vitro studies that used human breastmilk as a cell source of stem cells and clearly explained the step-by-step procedure. From the initial 457 studies, 15 articles fulfilled the criteria and were further analyzed. The results showed that the stem cells could be taken from breastmilk in any lactation stage and isolated with various techniques to obtain both pluri- and multipotent stem cells. Although breastmilk can be used as an alternative for noninvasive source of stem cell, the results of few study groups were found sometimes contradicting another group, resulting in confusing theory. Therefore, the standard protocol is still needed to tackle the confounding results.

Penggunaan pengawet non pangan formalin pada bahan makanan saat ini sudah banyak digunakan. Salah satu cara yang digunakan oleh pedagang ikan dalam proses pengawetan, yaitu dengan menggunakan formalin untuk menghambat terjadinya proses pembusukan dan kemunduran mutu ikan oleh mikroorganisme. Formalin dapat menimbulkan efek jangka pendek dan panjang pada kesehatan. Kandungan formalin pada ikan dapat diidentifikasi dengan uji kualitatif dan uji kuantitatif. Metode uji kualitatif formalin yang memiliki tingkat keakuratan tinggi dan spesifik pada sampel ikan segar saat ini belum dilaporkan. Oleh karena itu dilakukan penelitian yang bertujuan untuk menentukan metode kualitatif formalin yang paling akurat dan sesuai untuk identifikasi formalin pada sampel ikan tongkol. Penelitian ini menggunakan 5 metode uji kualitatif diantaranya asam kromatofat (K10H8O8S2), Tollens, KMnO4 0,1 N, Schiff, dan Fehling pada sampel ikan tongkol yang dijual dibeberapa Pasar Tradisional Yogyakarta. Berdasarkan hasil penelitian, tingkat sensitivitas dari 5 metode uji kualitatif formalin yang digunakan pada 15 sampel ikan tongkol yang paling tinggi adalah metode pereaksi Schiff.

Coffee fruit skin contains antioxidant compounds that can repair damaged tissues, especially those of reproductive or-gans. This study was designed to assess to what extent the metha-nolic extract of coffee fruit skin affected sperm characteristics and testicular histology in mice receiving 15% ethanol for 15 days. It used 25 male mice aged four months and employed a completely randomized design with two controls (K) and three treatments (P), namely K1 (without ethanol), K2 (15% ethanol), P1 (15% ethanol and the methanolic extract of coffee fruit skin, or MECS, at 125 mg/ kg BW), P2 (15% ethanol and MECS 250 mg/kg BW), and P3 (15% ethanol and MECS 500 mg/kg BW). These treatments were administered orally with a 1 mL disposable syringe for 15 days. The parameters observed were sperm characteristics (viability, morphology, and sperm count) and the microscopic structure of the testicles (lu-men area, diameter, and area of seminiferous tubules). These data were then analyzed using the one-way ANOVA, continued with the LSD and Duncan’s tests (P

Yam bean (Adult male mice were assigned to four groups (8 each), namely a normal diet-fed group (ND), HFD-fed group, and HFD supplemented with YBF groups (HFD + YBF) at a dose of 2.5% and 10%, respectively. Treatments were implemented for ten weeks. Thereafter, indicators of metabolic diseases, oxidative stress, inflammation, and gut microbiota composition were determined.A dosage of 10% YBF significantly inhibited excessive body weight gain (2.3 times lower than HFD group) and white adipose tissue (WAT) mass (2.2 times lower than HFD group) while sustaining brown adipose tissue mass. YBF prevented malondialdehyde elevation, catalase activity reduction, and expression of the interleukin-6 increment (2.7 times lower than the HFD group) within the WAT. Furthermore, YBF sustained normoglycaemia, glucose tolerance, and insulin sensitivity while precluding hyperinsulinemia. YBF modulated the gut microbiota community by increasing health-promoting microbiota includingYBF at the dose of 10% is proved to be useful in the prevention of diet-induced metabolic diseases, microbiota dysbiosis, and inflammation. Hence, YBF is recommended as a potential natural-based remedy to diminish the detrimental effects of high-fat foods.

Background and aims: Edible fiber isolated from the tuber of yam bean (Pachyrhizus erosus, Leguminosae) has been suggested to prevent the development of metabolic diseases caused by excessively consuming sugary foods. However, it is unclarified whether P. erosus fiber (PEF) is also capable of preventing liver diseases. This study aimed to determine the effectivity of PEF in counteracting the development of non-alcoholic fatty liver disease (NAFLD) caused by excessive intake of high-sugar diet (HSD). Material and method: 25% of PEF in HSD (w/w) was fed in BALB/c mice for eight weeks followed by subsequent morphological and histological examinations of the liver at the end of treatment in comparing with HSD alone. Results: We found that supplementation of 25% PEF sustained the normal morphological feature of the liver in HSD-fed mice. Moreover, PEF also prevented the development of microvesicles in the liver tissue, nuclear shrinkage, and hepatolysis as indicators of liver disease. Macrophages infiltration as a marker of liver inflammation was also less observed in PEF-treated mice. Conclusions: PEF could effectively elicit a beneficial effect against NAFLD caused by HSD. Hence, PEF is suggested to be used as a potent supplemental diet to preclude the metabolic diseases caused by HSD.

Objective: High number of antibiotic resistance cases in livestock will impact on increasing cases of microbe’s infection. On the other hand, the use of synthetic antibiotics is currently limited. A possible alternative can be used is the utilization of foods that possess medicinal effects (nutraceuticals). The use of animal feed sourced from Diptera larvae has been increasing widely, due to its high protein content. In addition, it is comprised of nutraceuticals as antimicrobial peptides like lucifensin. This study aimed at determining the potential of lucifensin as a nutraceutical product for livestock based on bioinformatics study.Methods: This study is descriptive research. The lucifensin protein data was obtained from the Protein Data Bank (PDB). The protein relationship analysis was performed using Blast-NCBI and lipinski Rules of 5 (Ro5) analysis to determine its potential as an oral drug (bioavailability). The molecular docking was used Swiss Docking online with lucifensin as target protein and Lipoteichoic Acid (LTAs) of Staphyllococus aureus as ligand.Results: The relationship analysis results showed that the lucifensin protein was related to two proteins of the other orders of diptera such as phormicin and sapecin. This protein belongs to the defensin protein family in which its coding genes are conserved until the order level. The Ro5 results showed that the mass of lucifensin protein was 312 daltons, its high lippopolycity was -0.5, it has five hydrogen bond donors, six hydrogen bond acceptors, and its molar refractivity was 77.14. Toxicity test also showed that this protein is classified as a safe component, and the docking results illustrate a strong energy bond that plays an important role in antimicrobial activity.Conclusions: In conclusion, lucifensin protein in the Lucilia sp. larvae is potential to be used as a livestock nutraceutical source that acts as an antimicrobial peptide.

AIM: Jicama (Pachyrhizus erosus, Fabaceae) has been promoted as a potent tuberous plant exerting both preventive and therapeutic effects against many diseases. In this present study, we aimed to investigate the pancreoprotective effect of isolated jicama fiber (JF) against glucotoxicity caused by high-sugar diet (HSD). METHODS: We performed an animal experimental research using adult male BALB/c mice with a completely randomized design consisted of four treatments and six replications. The treatments were diet types such as normal diet and HSD, supplemented with 10% and 25% of JF, respectively. The treatments were deployed for 8 weeks. Furthermore, random and fasting blood glucose levels were measured; histopathological alterations of pancreas including pancreatic adiposity, size of islet area, total cell number per islet, and necrosis level of pancreatic acinar cells were examined. Quantitative data were analyzed using an ANOVA followed by Duncan’s new multiple range test (p < 0.05). RESULTS: Our results demonstrate that supplementation of JF 10% and 25% improved blood glucose profile and significantly reduced inter pancreatic adiposity caused by HSD. Moreover, JF at the dose of 25% effectively sustained normal size of the islet of Langerhans and total cell number of the islet in pancreas of HSD-fed mice. JF 25% was also effective to counteract necrosis of pancreatic acinar cells. CONCLUSION: Our findings clarify a protective effect of JF, particularly at a dose of 25%, on pancreatic tissues against degeneration caused by HSD. Hence, JF is reliable to be a supplement counteracting the development of diabetes mellitus and associated diseases.

Laminin, a major basement membrane protein, comprises three subunit chains: α, β, and γ chains. Among these chains, only the laminin α chain is capable of signaling via laminin receptors. Although laminin isoforms containing the α5 chain were reported to be the first laminin produced during rat anterior pituitary gland development, the functions of these isoforms are unknown. We used immunohistochemical techniques to localize the laminin α5 chain and its specific receptor, basal cell adhesion molecule (BCAM), in fetal and adult pituitary gland. Laminin α5 chain immunoreactivity was observed in the basement membrane of the primordial adenohypophysis at embryonic days 12.5 to 19.5. Double immunostaining showed that BCAM was present and co-localized with the laminin α5 chain in the tissue. Quantitative analysis showed that the laminin α5 chain and BCAM were expressed in the anterior pituitary gland during postnatal development and in adulthood (postnatal day 60). In the adult gland, co-localization of the laminin α5 chain and BCAM was observed, and BCAM was detected in both the folliculo-stellate cells and endothelial cells. These results suggest that laminin α5 chain signaling via BCAM occurs in both the fetal adenohypophysis and adult anterior pituitary gland.

Jicama (Pachyrhizuz erosus, Fabaceae) has been reported to elicit various medicinal benefits against metabolic disturbances. We also have previously demonstrated that extracted jicama fiber (JF) could sustain normoglycemic state in high-sugar diet fed mice. In this present study, we investigated the effectivity of jicama fiber in preventing the dysregulation of energy metabolism as well as adiposity in adult male BALB/c mice fed with a high-fat diet (HFD). Three groups of animals were treated with normal diet (ND), HFD, and HFD in combination with 25% JF (w/w), respectively for 8 weeks ad libitum. Furthermore, food intake, energy intake, water intake, white adipose (WAT) and brown adipose (BAT) tissue mass, kidney and liver weight as well as organ index were determined. Our investigation revealed that JF 25% could preclude the perturbation of circadian feeding and energy intake rhythms caused by HFD but significantly reduced total water intake. JF also effectively counteracted the marked increase of WAT and decrease of BAT weight and its index in HFD fed mice. Furthermore, JF did not significantly alter the weight and index of both kidney and liver in HFD fed mice. This finding suggests that JF could be used as a potent supplement to minimize the disruption of energy homeostasis and obesity caused by HFD.

Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

Retinoic acid (RA) is converted from retinal by retinaldehyde dehydrogenases (RALDHs) and is an essential signaling molecule in embryonic and adult tissue. We previously reported that RALDH1 was produced in the rat anterior pituitary gland and hypothesized that RA was generated in the gland. Midkine (MK) is an RA-inducible growth factor, and MK production in the rat anterior pituitary gland was recently reported. However, the mechanism that regulates gene expression of MK in the pituitary gland has not been determined. To investigate regulation of MK production in the anterior pituitary gland, we analyzed changes in MK mRNA in cultured rat anterior pituitary cells. We identified MK-expressing cells by double-staining with in situ hybridization and immunohistochemical techniques for RALDH1. MK mRNA was expressed in RALDH1-producing cells in the anterior pituitary gland. Using isolated anterior pituitary cells of rats, we examined the effect of RA on gene expression of MK. Quantitative real-time PCR revealed that 72 h exposure to a concentration of 10-6 M of retinal and all-trans retinoic acid increased MK mRNA levels by about 2-fold. Moreover, the stimulatory effect of all-trans retinoic acid was mimicked by the RA receptor agonist Am80. This is the first report to show that RA is important in regulating MK expression in rat anterior pituitary gland.

Midkine (MK) belongs to a family of secreted heparin-binding growth factors and is highly expressed in various tissues during development. MK has multiple functions, such as regulation of cell proliferation, migration, survival and differentiation. We recently reported that MK mRNA is strongly expressed in the developing rat pituitary gland. In the adult pituitary, however, expression of MK and its receptor and the characteristics of the cells that produce them, have not been determined. Therefore, in this study, we investigate whether MK and its receptor, protein tyrosine phosphatase receptor-type Z (Ptprz1), are present in the adult rat pituitary. In situ hybridization, real-time reverse transcription-PCR and immunoblotting were performed to assess MK and Ptprz1 expression. We also characterize MK- and Ptprz1-expressing cells by double-staining with in situ hybridization and immunohistochemical techniques for each pituitary hormone or S100 protein [a marker of folliculostellate (FS) cells]. MK-expressing cells were located in the anterior and posterior lobes but not in the intermediate lobe. Double-staining and immunoblotting revealed that MK mRNA and protein were only expressed in FS cells in the anterior pituitary. Regarding Ptprz1 expression, Ptprz1 mRNA was detected in adrenocorticotropic hormone (ACTH) cells and growth hormone (GH) cells but not in prolactin cells, thyroid-stimulating hormone cells, luteinizing hormone cells, or FS cells. These findings suggest that MK produced in FS cells acts locally on ACTH cells and GH cells via Ptprz1 in the adult rat anterior pituitary.

Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke's pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.

The anterior pituitary gland is organized tissue comprising hormone-producing cells and folliculostellate (FS) cells. FS cells interconnect to form a meshwork, and their cytoplasmic processes are anchored by a basement membrane containing laminin. Recently, we developed a three-dimensional (3D) cell culture that reproduces this FS cell architecture. In this study of the novel function of FS cells, we used transgenic rats that express green fluorescent protein in FS cells for the 3D culture. Anterior pituitary cells were cultured with different proportions of FS cells (0%, 5%, 10%, and 20%). Anterior pituitary cells containing 5-20% FS cells formed round/oval cell aggregates, whereas amorphous cell aggregates were formed in the absence of FS cells. Interestingly, immunohistochemistry showed laminin-immunopositive cells instead of extracellular laminin deposition in FS cell-deficient cell aggregates. Double-immunostaining revealed that these laminin-immunopositive cells were gonadotrophs. Laminin mRNA expression did not differ in relation to the presence or absence of FS cells. When anterior pituitary cells with no FS cells were cultured with FS cell-conditioned medium, the proportion of laminin-immunopositive cells was lower than in control. These results suggest that a humoral factor from FS cells is required for laminin release from gonadotrophs.

The extracellular matrix (ECM) is important in creating cellular environments in tissues. Recent studies have demonstrated that ECM components are localized in anterior pituitary cells and affect cell activity. Thus, clarifying the mechanism responsible for ECM maintenance would improve understanding of gland function. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases and participate in ECM degradation. In this study, we investigated whether cells expressing TIMPs are present in rat anterior pituitary gland. Reverse transcription polymerase chain reaction was used to analyze expression of the TIMP family (TIMP1-4), and cells producing TIMPs in the gland were identified by using in situ hybridization. Expression of TIMP1, TIMP2, and TIMP3 mRNAs was detected, and the TIMP-expressing cells were located in the gland. The TIMP-expressing cells were also investigated by means of double-staining with in situ hybridization and immunohistochemical techniques. Double-staining revealed that TIMP1 mRNA was expressed in folliculostellate cells. TIMP2 mRNA was detected in folliculostellate cells, prolactin cells, and thyroid-stimulating hormone cells. TIMP3 mRNA was identified in endothelial cells, pericytes, novel desmin-immunopositive perivascular cells, and folliculostellate cells. These findings indicate that TIMP1-, TIMP2-, and TIMP3-expressing cells are present in rat anterior pituitary gland and that they are involved in maintaining ECM components.

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