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Postbiotic metabolites produced by Lactiplantibacillus plantarum strains isolated from Malaysian food have been extensively reported for their positive effects on health. Understanding the effects of different combinations of carbon and nitrogen sources on the growth and corresponding characteristics of postbiotic metabolites produced by different strains of L. plantarum is important for various applications. Hence, the effects of different combinations of carbon (glucose, lactose, sucrose and dextrose) and nitrogen (X-SEED Kat, X-SEED Peptone, X-SEED Nucleo Advanced, Nucel875 MG, FM888 and FM902) sources on the growth of six strains of L. plantarum (RG11, RG14, RI11, RS5, TL1 and UL4) and the functional characteristics (bacteriocin inhibitory activity, antioxidant activity and lactic acid concentration) of their respective postbiotic metabolites were investigated in this study. UL4 produced the highest viable cell population with sucrose and Nucel875 nitrogen source. The UL4 strain also produced the strongest bacteriocin inhibitory activity with dextrose and FM888 nitrogen source. In comparison, the RI11 strain produced the highest lactic acid concentration with dextrose and Nucel875 nitrogen source and the highest reducing power of RS5 and TL1 postbiotic metabolites was achieved with MRS medium. In the combination of sucrose and X-Seed KAT nitrogen source, RG14 produce the highest hydroxyl radical scavenging activity. The effects of different combinations of carbon and nitrogen sources on the viable cell population of L. plantarum strains and the respective functional characteristics of postbiotic metabolites were strain dependent. The current study also revealed that fermentation media were an important factor that greatly impacted the functionalities of postbiotic metabolites due to the presence of various bioactive compounds that contributed to high antioxidant and antimicrobial properties. The results of this study will facilitate the subsequent medium design and optimisation for the development and production of specific postbiotic metabolites produced by the respective L. plantarum strain for their applications in various industries.

Abstract Poly(ADP-ribose) polymerase (PARP) are critical DNA repair enzymes that are activated as part of the DNA damage response (DDR). Although inhibitors of PARP (PARPi) have emerged as small molecule drugs and have shown promising therapeutic effects, PARPi used as single agents are clinically limited to patients with mutations in germline breast cancer susceptibility gene (BRCA). Thus, novel PARPi combination strategies may expand their usage and combat drug resistance. In recent years, ruthenium polypyridyl complexes (RPCs) have emerged as promising anti-cancer candidates due to their attractive DNA binding properties and distinct mechanisms of action. Previously, we reported the rational combination of the RPC DNA replication inhibitor [Ru(dppz)2(PIP)]2+ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine, PIP = 2-(phenyl)-imidazo[4,5-f][1,10]phenanthroline), “Ru-PIP”, with the PARPi Olaparib in breast cancer cells. Here, we expand upon this work and examine the combination of Ru-PIP with Olaparib for synergy in lung cancer cells, including in 3D lung cancer spheroids, to further elucidate mechanisms of synergy and additionally assess toxicity in a zebrafish embryo model. Compared to single agents alone, Ru-PIP and Olaparib synergy was observed in both A549 and H1975 lung cancer cell lines with mild impact on normal lung fibroblast MRC5 cells. Employing the A549 cell line, synergy was confirmed by loss in clonogenic potential and reduced migration properties. Mechanistic studies indicated that synergy is accompanied by increased double-strand break (DSB) DNA damage and reactive oxygen species (ROS) levels which subsequently lead to cell death via apoptosis. Moreover, the identified combination was successfully able to inhibit the growth of A549 lung cancer spheroids and acute zebrafish embryos toxicity studies revealed that this combination showed reduced toxicity compared to single-agent Ru-PIP.

Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H2O2), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as ‘kesum’, is widely used in traditional medicine. P. minus has been reported to exhibit a few medicinal and pharmacological properties. The current study aimed to investigate the neuroprotective effects of P. minus ethanolic extract (PMEE) on H2O2-induced neurotoxicity in SH-SY5Y cells. LC–MS/MS revealed the presence of 28 metabolites in PMEE. Our study showed that the PMEE provided neuroprotection against H2O2-induced oxidative stress by activating the Nrf2/ARE, NF-κB/IκB and MAPK signaling pathways in PMEE pre-treated differentiated SH-SY5Y cells. Meanwhile, the acetylcholine (ACH) level was increased in the oxidative stress-induced treatment group after 4 h of exposure with H2O2. Molecular docking results with acetylcholinesterase (AChE) depicted that quercitrin showed the highest docking score at −9.5 kcal/mol followed by aloe-emodin, afzelin, and citreorosein at −9.4, −9.3 and −9.0 kcal/mol, respectively, compared to the other PMEE’s identified compounds, which show lower docking scores. The results indicate that PMEE has neuroprotective effects on SH-SY5Y neuroblastoma cells in vitro. In conclusion, PMEE may aid in reducing oxidative stress as a preventative therapy for neurodegenerative diseases.

Since lung cancer is the leading cause of cancer-related death worldwide, research is being conducted to discover anticancer agents as its treatment. Eleutherine bulbosa, a Dayak folklore medicine, exhibited anticancer effects against several cancer cells; however, its anticancer potency against lung cancer cells has not been explored yet. This study aims to determine the anticancer potency of E. bulbosa bulbs against lung cancer cells (A549) using 2D and 3D culture models, as well as determine its active compounds using gas chromatography-mass spectrometry (GC-MS) analysis. Three fractions of E. bulbosa bulbs, namely chloroform, n-hexane, and ethyl acetate, were tested for cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) and CellTiter-Glo. The antiproliferative effects of the most cytotoxic fraction against the 2D culture model were determined by a clonogenic survival assay and propidium iodide/Hoechst 33342 double staining, whereas the effects against the 3D culture model were determined by microscopy, flow cytometry, and gene expression analysis. The chloroform fraction is the most cytotoxic against A549 cells than other fractions, and it inhibited colony formation and induced apoptosis of A549 cells. The chloroform fraction also inhibited the growth of the A549 spheroid by suppressing the spheroid size, inducing apoptosis, reducing the proportion of CD44 lung cancer stem cells, causing arrest at the S phase of the cell cycle, and suppressing the expression of the SOX2 and MYC genes. Furthermore, the GC-MS analysis detected 20 active compounds in the chloroform fraction, including the major compounds of eleutherine and isoeleutherine. In conclusion, the chloroform fraction of E. bulbosa bulbs exhibit its antiproliferative effect on 2D and 3D culture models of A549 cells, suggesting it could be a lung cancer chemopreventive agent.

Wounds are considered to be a serious problem that affects the healthcare sector in many countries, primarily due to diabetes and obesity. Wounds become worse because of unhealthy lifestyles and habits. Wound healing is a complicated physiological process that is essential for restoring the epithelial barrier after an injury. Numerous studies have reported that flavonoids possess wound-healing properties due to their well-acclaimed anti-inflammatory, angiogenesis, re-epithelialization, and antioxidant effects. They have been shown to be able to act on the wound-healing process via expression of biomarkers respective to the pathways that mainly include Wnt/β-catenin, Hippo, Transforming Growth Factor-beta (TGF-β), Hedgehog, c-Jun N-Terminal Kinase (JNK), NF-E2-related factor 2/antioxidant responsive element (Nrf2/ARE), Nuclear Factor Kappa B (NF-κB), MAPK/ERK, Ras/Raf/MEK/ERK, phosphatidylinositol 3-kinase (PI3K)/Akt, Nitric oxide (NO) pathways, etc. Hence, we have compiled existing evidence on the manipulation of flavonoids towards achieving skin wound healing, together with current limitations and future perspectives in support of these polyphenolic compounds as safe wound-healing agents, in this review.

The reduction of graphene oxide (rGO) utilizing green methods such as plants has attracted much attention due to its productivity, eco—friendly features, and cost effectiveness. In the present study, the reflux method was employed to synthesize Clinacanthus nutans (C. nutans) leaf extract mediated rGO using a simple approach. The synthesized rGO was characterized using various spectroscopic and microscopic techniques. The UV-Vis spectrum demonstrated the absorption peak of rGO (270 nm) at distinct locations, while the FTIR analysis demonstrated that the amount of oxygen group in rGO was reduced. The Raman analysis confirms the reduction of GO by a slight increase in the D—band to G—band intensity ratio. The XRD spectra demonstrated that rGO was successfully produced based on the illustrated 2Ɵ angles at a peak of 22.12° with d-spacing of 0.40 nm. FESEM clearly reveals the morphology of rGO that shows crumpled thin sheets, a rougher surface, and a wave—shaped corrugated structure. The reduction of GO was analyzed in the removal of the hydroxyl group and amorphotization of sp2 carbon structures. The C/O ratio in rGO was higher than GO which indicates the small amount of oxygen-containing functional groups were still presented in the reduced graphene oxide. Furthermore, the cyclic voltammetry behavior of a modified screen—printed carbon electrode (SPCE) was measured. The redox reactivity of rGO—SPCE has been affirmed and compared with GO—SPCE and bare—SPCE. The toxicity using A. salina cysts demonstrated that rGO is less toxic compared to GO. The analysis adequately supports the synthesis of rGO and the effective removal of oxygen-containing functional groups from GO. The findings herein illustrate that C. nutans mediates the synthesis of rGO and is a promising eco-friendly substitute to conventional carbon-based fabrication.

Objective: To compare endometrial thickness after three consecutive cycles of ovulation induction with clomiphene citrate versus letrozole. Methods: Eighty-four women with normal menstrual interval who attended the university infertility clinic from June 2016 to March 2017 were eligible for the study. After the endometrial thickness of baseline cycle was recorded, all participants were randomized into two groups of clomiphene citrate or letrozole treatment for three consecutive cycles. Endometrial thickness and estradiol level were measured when at least one follicle reached 17 mm in diameter. The differences in endometrial thickness relative to baseline of the two groups were compared. Results: A total of 62 patients completed three cycles of ovarian stimulation. Both drugs resulted in significantly thinner endometrium compared with the baseline cycle thickness. The mean endometrial thickness was significantly decreased in the clomiphene citrate group compared with letrozole group (7.46 ± 1.71 vs 8.88 ± 2.34 mm, p = 0.029). Estradiol level on the day of induced ovulation was significantly higher in the clomiphene citrate group than in the letrozole group (706.0 (207.9, 2209.0) vs 168.7 (30.0, 401.8), p < 0.001). The number of the follicles reaching 17 mm on the day of induced ovulation was higher in the clomiphene citrate group (1.9 ± 0.8 vs 1.4 ± 0.5, p = 0.002). Conclusion: Letrozole had less effect on endometrium thinning after three consecutive cycles of induced ovulation compared with clomiphene citrate.

Objective: To compare obstetric and perinatal outcomes between singletons born after IVF and natural conception. Methods: A total of 141 singleton pregnancies conceived by IVF were included. Another 141 singleton pregnancies conceived naturally were randomly selected as comparison group, matched by age. Data were retrospectively extracted from medical records, including baseline characteristics and delivery data. Various characteristics, including pregnancy and neonatal outcomes were compared between groups. Results: Women in IVF group were more likely to be nulliparous and had previous miscarriage (88.7% vs. 76.6%, 0=0.003; and 26.2% vs. 14.8%, p=0.018, respectively). Underlying diseases and complications during pregnancy were comparable between the 2 groups. Mean gestational age was lower in IVF group (37.9 ± 2.0 vs. 38.4 ± 1.6, p=0.008), but without clinical significance. Primary cesarean section was significantly more common among women in IVF group (74.4% vs. 54.6%, p

Natural product is an excellent candidate for alternative medicine for disease management. The bulb of E. bulbosa is one of the notable Iridaceae family with a variety therapeutic potential that is widely cultivated in Southeast Asia. The bulb has been used traditionally among the Dayak community as a folk medicine to treat several diseases like diabetes, breast cancer, nasal congestion, and fertility problems. The bulb is exceptionally rich in phytochemicals like phenolic and flavonoid derivatives, naphthalene, anthraquinone, and naphthoquinone. The electronic database was searched using various keywords, i.e., E. bulbosa, E. americana, E. palmifolia, E. platifolia, and others due to the interchangeably used scientific names of different countries. Scientific investigations revealed that various pharmacological activities were recorded from the bulb of E. bulbosa including anti-cancer, anti-diabetic, anti-bacterial, anti-fungi, anti-viral, anti-inflammatory, dermatological problems, anti-oxidant, and anti-fertility. The potential application of the bulb in the food industry and in animal nutrition was also discussed to demonstrate its great versatility. This is a compact study and is the first study to review the extensive pharmacological activities of the E. bulbosa bulb and its potential applications. The development of innovative food and pharma products from the bulb of E. bulbosa is of great interest.

Inositol hexaphosphate (IP6), or phytic acid is a natural dietary ingredient and has been described as a “natural cancer fighter”, being an essential component of nutritional diets. The marked anti-cancer effect of IP6 has resulted in our quest for an understanding of its mechanism of action. In particular, our data provided strong evidence for the induction of apoptotic cell death, which may be attributable to the up-regulation of Bax and down-regulation of Bcl-xl in favor of apoptosis. In addition, the up-regulation of caspase-3 and -8 expression and activation of both caspases may also contribute to the apoptotic cell death of human colorectal adenocarcinoma HT-29 cells when exposed to IP6. Collectively, this present study has shown that rice bran IP6 induces apoptosis, by regulating the pro- and anti-apoptotic markers; Bax and Bcl-xl and via the activation of caspase molecules (caspase-3 and -8).

Abstract Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of β-catenin and COX-2 reduced significantly (p < 0.05) in all the groups treated with GBR (G2, G3 and G4) compared to the control group (G1). Spearman rank correlation test showed significant positive linear relationship between total β-catenin and COX-2 score (Spearman's rho = 0.616, p = 0.0001). It is demonstrated that GBR inhibits the development of total number of ACF and AC, and multicrypt of ACF, reduces the expression of β-catenin and COX-2, and thus can be a promising dietary supplement in prevention of colon cancer.

Phytochemicals and other natural products have been suggested to be effective adjuvants to conventional therapy to reduce potential side effects that arise from cancer treatments. Various natural compounds and synthetic analogues have been studied for their potential anti-cancer properties in the last decade. Prior to administering them to patients in a clinical setting, drug development necessitates a sequence of preclinical testing, beginning with in vitro and progressing to in vivo studies. While numerous drugs and plant extracts were reported to be active in vitro, only several of them had reproducible activity at the tested doses in vivo. Furthermore, breakthroughs in manipulating gene editing have aided scientists in accurately replicating human diseases in animal models. Therefore, during drug development, in vivo studies are of tremendous help in evaluating a drug candidate's safety, toxicity, and efficacy in complex physiological and biochemical states. Hence, for this purpose, it is crucial to apply and select the animal model that is the most suitable to represent the studied disease or biological process. The current review summarizes various animal models that have been considered for in vivo testing, their advantages and disadvantages, and the experimental guidelines for conducting animal studies.

Chemoprevention has become an important area in cancer research due to the failure of current therapeutic modalities. Epidemiological and preclinical studies have demonstrated that nutrition plays a vital role in the etiology of cancer. This study was conducted to determine the chemopreventive effects of germinated brown rice (GBR) in rats induced with colon cancer. GBR is brown rice that has been claimed to be richer in nutrients compared to the common white rice. The male Sprague Dawley rats (6 weeks of age) were randomly divided into 5 groups: (G1) positive control (with colon cancer, unfed with GBR), (G2) fed with 2.5 g/kg of GBR (GBR (g)/weight of rat (kg)), (G3) fed with 5 g/kg of GBR, (G4) fed with 10 g/kg of GBR and (G5) negative control (without colon cancer, unfed with GBR). GBR was administered orally once daily via gavage after injection of 15 mg/kg of body weight of azoxymethane (AOM) once a week for two weeks, intraperitonially. After 8 weeks of treatment, animals were sacrificed and colons were removed. Colonic aberrant crypt foci (ACF) were evaluated histopathologically. Total number of ACF and AC, and multicrypt of ACF, and the expression of beta-catenin and COX-2 reduced significantly (p < 0.05) in all the groups treated with GBR (G2, G3 and G4) compared to the control group (G1). Spearman rank correlation test showed significant positive linear relationship between total beta-catenin and COX-2 score (Spearman's rho = 0.616, p = 0.0001). It is demonstrated that GBR inhibits the development of total number of ACF and AC, and multicrypt of ACF, reduces the expression of beta-catenin and COX-2, and thus can be a promising dietary supplement in prevention of colon cancer. [ABSTRACT FROM AUTHOR]