Meta-analysis of the effects of gamma irradiation on chicken meat and meat product quality.

Background and Aim: Irradiation is one of the most effective microbial decontamination treatments for eliminating foodborne pathogens and enhancing chicken meat safety. The effect of gamma irradiation on the overall quality of chicken meat and its products must be observed to provide a comprehensive explanation to the public. This meta-analysis examined the effects of gamma irradiation on the oxidation parameters, microbial activity, physicochemical characteristics, sensory parameters, and nutrient quality of chicken meat and meat products. Materials and Methods: We conducted a literature search using various search engines (Scopus®, PubMed®, and Google Scholar®) with "irradiation," "gamma," "chicken," and "meat" as keywords. Gamma irradiation treatment was set as a fixed effect, and the difference between experiments was set as a random effect. This study used a mixed-model methodology. After evaluation, we selected 43 articles (86 studies) for inclusion in the database. Results: Gamma irradiation significantly increased (p < 0.01) thiobarbituric acid-reactive substance levels on days 0, 7, and 14 of storage. Gamma irradiation reduced total aerobic bacteria, coliforms, Salmonella, yeast, and mold activity (p < 0.01). According to our meta-analysis, 21.75 kGy was the best dose for reducing total aerobic bacteria. On day 0, gamma irradiation did not affect the color parameters (L*, a*, b*). However, a significant difference (p < 0.01) was noted for a* and b* parameters between the control and irradiation treatments at 7 and 14 days. Although irradiation treatment was less consistent in sensory parameters, overall acceptability decreased on days 0, 7, and 14 after storage (p < 0.05). Regarding nutrient composition, gamma irradiation reduced moisture content and free fatty acid (FFA) content (p < 0.05). Although irradiation significantly reduces the microbial population, it increases the oxidation of chicken meat and its products. Irradiation decreases FFA content and overall acceptability, but it does not affect flavor, tenderness, juiciness, or cooking loss. Conclusion: Gamma irradiation positively reduces the microbial activity in chicken meat and its products but increases the oxidation parameters. Although gamma irradiation does not alter the flavor, tenderness, juiciness, or cooking loss, gamma irradiation can reduce the FFA content and overall acceptability.

N-phenyl pyrazoline derivative inhibits cell aggressiveness and enhances paclitaxel sensitivity of triple negative breast cancer cells.

Protein kinase dysregulation induces cancer cell aggressiveness leading to rapid tumor progression and poor prognosis in TNBC patients. Many small-molecule kinase inhibitors have been tested in clinical trials to treat TNBC patients. In the previous study, we found that N-phenylpyrazoline small molecule acts as a protein kinase inhibitor in cervical cancer cells. However, there remains unknown about N-phenyl pyrazoline potency as a kinase inhibitor and its anti-cancer activity in TNBC cells. In this study, we investigated the activity of N-phenyl pyrazoline against TNBC cells via tyrosine kinase inhibition. Based on the MTT assay, the IC50 values for the N-phenyl pyrazoline 2, 5, A, B, C, and D against Hs578T were 12.63 µM, 3.95 µM, not available, 18.62 µM, 30.13 µM, and 26.79 µM, respectively. While only P5 exhibited the IC50 against MDA MB 231 (21.55 µM). Further, N-phenyl pyrazoline 5 treatment significantly inhibited the cell proliferation rate of Hs578T and MDA MB 231 cells. The migration assay showed that treatment with the compound N-phenyl pyrazoline 5 with 4 µM concentration significantly reduced cell migration of Hs578T cells. N-phenyl pyrazoline 5 treatment at 1 µM and 2 µM was able to reduce the tumorsphere size of Hs578t cells. A combination treatment of P5 and paclitaxel showed a synergistic effect with a combination index score > 1 in both TNBC cells. Further, the P5 predictively targeted the protein kinases that significantly correlated to breast cancer prognosis. The GSEA analysis result shows that receptor tyrosine kinase, Notch3, Notch4, and Ephrin signaling pathways were targeted by P5. The P5 treatment reduced the EGFR expression level and activation in TNBC cells.

Pyrazoline B-Paclitaxel or Doxorubicin Combination Drugs Show Synergistic Activity Against Cancer Cells: In silico Study.

Background: Multidrug resistance in various cancer types is a major obstacle in cancer treatment. The concept of a single drug molecular target often causes treatment failure due to the complexity of the cellular processes. Therefore, combination chemotherapy, in which two or more anticancer drugs are co-administered, can overcome this problem because it potentially have synergistic efficacy besides reducing resistance, and drug doses. Previously, we reported that pyrazoline B had promising anticancer activity in both in silico and in vitro studies. To increase the efficacy of this drug, co-administration with established anticancer drugs such as doxorubicin and paclitaxel is necessary. Materials and Methods: In this study, we used an in silico approach to predict the synergistic effect of pyrazoline B with paclitaxel or doxorubicin using various computational frameworks and compared the results with those of an established study on the combination of doxorubicin-cyclophosphamide and paclitaxel-ascorbic acid. Results and Discussion: Drug interaction analysis showed the combination was safe with no contraindications or side effects. Furthermore, molecular docking studies revealed that doxorubicin-pyrazoline B and doxorubicin-cyclophosphamide may synergistically inhibit cancer cell proliferation by inhibiting the binding of topoisomerase I to the DNA chain. Moreover, the combination of pyrazoline B-paclitaxel may has synergistic activity to cause apoptosis by inhibiting Bcl2 binding to the Bax fragment or inhibiting cell division by inhibiting α-ß tubulin disintegration. Paclitaxel-ascorbic acid had a synergistic effect on the inhibition of α-ß tubulin disintegration. Conclusion: The results show that this combination is promising for further in vitro and in vivo studies.

Isolation of active compounds from Streptomyces sennicomposti GMY01 and cytotoxic activity on breast cancer cells line.

The occurrence of resistance to anticancer and the emergence of serious side effects due to chemotherapy is one of the main problems in cancer treatment, including breast cancer. The need for effective anticancer with a specific target is urgently required. Streptomyces are widely known as the potential producers of new anticancer molecules. Previously reported that the methanol extract of Streptomyces sennicomposti GMY01 isolated from Krakal Coast, Gunungkidul had very strong cytotoxic activity against MCF-7 and T47D breast cancer cells with IC50 values of 0.6 and 1.3 µg/mL, respectively. The following study aimed to isolate and identify active compounds of the S. sennicomposti GMY01 and evaluate its cytotoxic activity. The study was started by re-culturing and re-fermented optimization of S. sennicomposti GMY01 in a larger volume, then the bacteria were extracted using methanol following the bioassay-guided isolation of the extract obtained. The active compounds obtained were then structurally determined using UV/Vis spectroscopy, Fourier Transform-Infrared (FT-IR), Liquid Chromatography-Mass Spectroscopy (LC-MS), 1H NMR, and 13C NMR and analyzed for their cytotoxic activity using MTT assay on MCF-7 and normal Vero cells line. The results showed that the culture of the S. sennicomposti GMY01 using Starch Nitrate Broth (SNB) media yields the best results compared to other culture media. An active anticancer compound namely mannotriose was successfully isolated from the methanol extract with an IC50 value of 5.6 µg/mL and 687 µg/mL against the MCF-7 and Vero cells lines, respectively, indicating that this compound showed strong cytotoxic activity with high selectivity.

Antibacterial and Angiotensin I-Converting Enzyme (ACE) Inhibition Activities of Essential Oil from Java Cardamom (Amomum compactum) Fruit.

The essential oil has been reported to be one of the Angiotensin I-Converting Enzyme (ACE) inhibitor resources. Moreover, it has been proven against bacterial pathogens that cause infectious diseases. Amomum compactum is one source of essential oil, known as Javanese cardamom is a spice herb commonly used for flavouring food and traditional medicine in Indonesia. However, ACE inhibition activity of A. compactum has not been reported. The purposes of this study were to identify the main constituent of volatile compounds, inhibition activity toward bacteria, and antihypertension potency of A. compactum essential oils. Volatile compounds were investigated using Gas Chromatography-Mass Spectrometry (GC-MS). The antimicrobial activity was observed using the microdilution method toward Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. The antihypertension effect was studied using an ACE inhibition assay. The result showed that eucalyptol was a primary compound of A. compactum fruit either in Banjar (BJR) and Bogor (BGR) essential oils with the value of 62.22% and 66.23%, respectively. Both BJR and BGR are more active to inhibit gram-positive bacteria (B. subtilis) with MIC values of 1 mg/mL. Meanwhile, the BJR exhibited a higher inhibitory activity effect toward ACE compared to BGR with the value of IC50 64.86 ± 0.57 µg/mL. These findings suggest that A. compactum essential oil can be the potential to lead to the treatment of hypertension as an ACE inhibitor and antibacterial agent. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01080-x.

Marine-Derived Streptomyces sennicomposti GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking.

To discover novel antimalarial and anticancer compounds, we carried out a genome analysis, bioassay, metabolite profiling, and molecular docking of marine sediment actinobacteria strain GMY01. The whole-genome sequence analysis revealed that Streptomyces sp. GMY01 (7.9 Mbp) is most similar to Streptomyces sennicomposti strain RCPT1-4T with an average nucleotide identity (ANI) and ANI based on BLAST+ (ANIb) values of 98.09 and 97.33% (>95%). An in vitro bioassay of the GMY01 bioactive on Plasmodium falciparum FCR3, cervical carcinoma of HeLa cell and lung carcinoma of HTB cells exhibited moderate activity (IC50 value of 46.06; 27.31 and 33.75 µg/mL) with low toxicity on Vero cells as a normal cell (IC50 value of 823.3 µg/mL). Metabolite profiling by LC-MS/MS analysis revealed that the active fraction of GMY01 contained carbohydrate-based compounds, C17H29NO14 (471.15880 Da) as a major compound (97.50%) and mannotriose (C18H32O16; 504.16903 Da, 1.96%) as a minor compound. Molecular docking analysis showed that mannotriose has a binding affinity on glutathione reductase (GR) and glutathione-S-transferase (GST) of P. falciparum and on autophagy proteins (mTORC1 and mTORC2) of cancer cells. Streptomyces sennicomposti GMY01 is a potential bacterium producing carbohydrate-based bioactive compounds with anti-plasmodial and anticancer activities and with low toxicity to normal cells.

Draft Genome Sequence of the Marine-Derived, Anticancer Compound-Producing Bacterium Streptomyces sp. Strain GMY01.

The marine Streptomyces sp. strain GMY01 was isolated from Indonesian marine sediment. Genome mining analysis revealed that GMY01 has 28 biosynthetic gene clusters, dominated by genes encoding nonribosomal peptide synthetase and polyketide synthase.

Soil-derived Streptomyces sp. GMR22 producing antibiofilm activity against Candida albicans: bioassay, untargeted LC-HRMS, and gene cluster analysis.

Biofilm-forming fungi, Candida albicans, are currently a serious problem in infectious disease cases. Soil bacteria Streptomyces sp. GMR22 have a large genome size and antifungal metabolites against C. albicans, but its potential antibiofilm activity is not clearly defined. The aims of this study were to determine the antibiofilm activity of GMR22 against C. albicans, identify the main constituents of active extracts, and investigate the biosynthesis gene clusters encoding the enzymes related to metabolism pathways. Antifungal and antibiofilm measurements were performed using in vitro assays on C. albicans ATCC 10231. Main constituents of active extracts were analyzed using untargeted Liquid Chromatography tandem High-Resolution Mass Spectrometry (LC-HRMS). RAST software was applied to investigate the gene clusters of the biosynthesis pathways based on whole genome sequences. Chloroform extract of GMR22 has antifungal and antibiofilm properties at 13-420 µg/mL with palmitic acid (C16H32O2, 273.27028 Da), a saturated fatty acid as a major constituent (42.74). Streptomyces sp. GMR22 has 53 subsystems related to fatty acids biosynthesis (Fab) FAS II. The Kyoto Encyclopedia of Gene and Genome map of Fab revealed 10 of 21 (47.6%) gene clusters encode enzymes related to Fab. There were six gene clusters encoding the enzymes related to the hexadecenoic acid (palmitic acid) biosynthesis pathways: 6.4.12; FabD, FabH, FabF, FabG, FabI and 1.14.192. Each enzyme was encoded by 3-14 genes. These results confirmed that soil Streptomyces sp. GMR22 bacterium has remarkable biotechnological potential by producing fatty acids which are mostly palmitic acid as an active antibiofilm agent against C. albicans.

Metabologenomics approach to the discovery of novel compounds from Streptomyces sp. GMR22 as anti-SARS-CoV-2 drugs.

COVID-19 is spreading rapidly yet there is no clinically proven drug available now. Soil-derived Streptomyces sp. GMR22 has a large genome size (11.4 Mbp) and a huge BGCs (Biosynthetic Gene Clusters) encoding secondary metabolites. This bacterium is a potential source for producing a wide variety of compounds which are able to block SARS-CoV-2, the causative agent of COVID-19. This study aimed to predict the secondary metabolites of Streptomyces sp. GMR22 and to evaluate the ability as SARS-CoV-2 inhibitor. The AntiSMASH 5.0 was used for genome mining analysis and targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) was used for metabolite analysis. In silico molecular docking was performed on important target proteins of SARS-CoV-2 i.e., spike protein (PDB ID: 6LXT), Receptor Binding Domain (RBD)-ACE2 (Angiotensin-Converting Enzyme 2) (PDB ID: 6VW1), 3CLpro (3-chymotrypsin-like protease) (PDB ID: 6M2N), and RdRp (RNA-dependent RNA polymerase) (PDB ID: 6M71). Two compounds from GMR22 extract, echoside A and echoside B were confirmed by targeted LC-HRMS and potential as SARS-CoV-2 inhibitor. Echoside A and echoside B showed higher docking score than remdesivir as COVID-19 drug on four target proteins, i.e., spike protein (-7.9 kcal/mol and -7.8 kcal/mol), RBD-ACE2 (-7.5 kcal/mol and -8.2 kcal/mol), 3CLpro (-8.4 kcal/mol and -9.4 kcal/mol) and RdRp (-7.3 kcal/mol and -8.0 kcal/mol). A combination of genome mining and metabolomic approaches can be used as integrated strategy to elucidate the potential of GMR22 as a resource in the discovery of anti-COVID -19 compound.

Complete Genome Sequence of Bacillus velezensis GMEKP1, Isolated from a Natural Bamboo Hive of Stingless Bees.

We report the complete genome sequence and annotation of Bacillus velezensis GMEKP1, which was isolated from a hive of stingless bees (Trigona laeviceps). This bacterium has a circular 4,014,839-nucleotide chromosome and two circular plasmids. Genome-mining analysis of the whole-genome sequence revealed that GMEKP1 has 12 biosynthetic gene clusters, dominated by genes encoding polyketide synthase hybrids.

Two strains of airborne Nocardiopsis alba producing different volatile organic compounds (VOCs) as biofungicide for Ganoderma boninense.

Nocardiopsis are actinobacteria which produce active compounds, such as antifungals and volatile compounds. Ganoderma boninense is a pathogenic and aggressive fungus that decreases palm oil yield during production. In this study, we isolated two strains of Nocardia (GME01 and GME22) from airborne contaminants on the actinobacteria culture collection in the laboratory. The aim of this study is to identify two strains of Nocardiopsis and to obtain the antifungal potency of volatile organic compounds (VOCs) against G. boninese. We characterized the morphology using Scanning Electrone Microscope (SEM), molecular properties and whole-cell protein spectra using Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS), antifungal assay on G. boninense and VOCs analysis of Nocardia using solid phase micro extraction/gas chromatography (SPME/GC). The two Nocardiopsis strains had the similar characteristic such as white aerial mycelium and spores, aerobic, grow well on ISP-2, TSA and NA medium without diffusible pigment and had the highest similarity with Nocardiopsis alba DSM 43377 (99.63% and 99.55% similarity for GME01 and GME22, respectively), Different morphological feature was found in aerial mycelium and spores. GME22 has a clearly fragmented mycelium whereas GME01 has none. Other features also showed different on the whole-cell protein spectra, antifungal activity and VOCs profiles. Antifungal activity assay on G. boninense showed that N. alba GME22 has higher antifungal activity than GME01 related with the VOCs abundance in two strains. Almost 38.3% (18 VOCs) of N. alba GME22 and 25.5% (12 VOCs) of N. alba GME01 were found specifically in each strain, and 36.2% (the 17 same VOCs) produced by both. The known volatile antifungal compounds S-methyl ethanethioate, 1,2-dimethyldisulfane, acetic acid, 2-methyl propanoic acid, 3-methyl-butanoic acid, nonan-2-one, undecan-2-one and 2-isopropyl-5-methylcyclohexan-1-ol only produced by N. alba GME22 and 1,3-dimethyltrisulfane only produced by N. alba GME01. A total of two known antifungal compounds 1,2-dimethyldisulfane and 6-methylheptan-2-one were produced by both N. alba. The abundance of antifungal VOCs produced by these bacteria is potentially to be used as biocontrol agent for pathogenic fungi in plants.

Potential secondary metabolite from Indonesian Actinobacteria (InaCC A758) against Mycobacterium tuberculosis.

OBJECTIVES: This study explored Indonesian Actinobacteria which were isolated from Curcuma zedoaria endophytic microbes and mangrove ecosystem for new antimycobacterial compounds. MATERIALS AND METHODS: Antimycobacterial activity test was carried out against Mycobacterium tuberculosis H37Rv. Chemical profiling of secondary metabolite using Gas Chromatography-Mass Spectroscopy (GC-MS) and High Resolution-Mass Spectroscopy (HR-MS) was done to the ethyl acetate extract of active strain InaCC A758. Molecular taxonomy analysis based on 16S rRNA gene and biosynthetic gene clusters analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) from InaCC A758 have been carried out. Bioassay guided isolation of ethyl acetate extract was done, then structural elucidation of active compound was performed using UV-Vis, FT-IR, and NMR spectroscopy methods. RESULTS: The chemical profiling using HR-MS revealed that InaCC A758 has the potential to produce new antimycobacterial compounds. The 16S rRNA gene sequencing showed that InaCC A758 has the closest homology to Streptomyces parvus strain NBRC 14599 (99.64%). In addition, InaCC A758 has NRPS gene and related to S. parvulus (92% of similarity), and also PKS gene related to PKS-type borrelidin of S. rochei and S. parvulus (74% of similarity). Two compounds with potential antimycobacterial were predicted as 1) Compound 1, similar to dimethenamid (C12H18ClNO2S; MW 275.0723), with MIC value of 100 µg/ml, and 2) Compound 2, actinomycin D (C62H86N12O16; MW 1254.6285), with MIC value of 0.78 µg/ml. CONCLUSION: Actinomycin D has been reported to have antimycobacterial activity, however the compound has been predicted to resemble dimethenamid had not been reported to have similar activity.

Complete Genome Sequence of the Marine-Derived Bacterium Streptomyces sp. Strain GMY02.

We report the complete genome sequence of Streptomyces sp. strain GMY02, isolated from Indonesian marine sediment. This bacterium has a circular 8,512,626-nucleotide chromosome. Genome mining analysis of the whole-genome sequence revealed that GMY02 has 28 biosynthetic gene clusters, dominated by genes encoding nonribosomal peptide synthetase and polyketide synthase.

Polyherbal formula (ASILACT®) induces Milk production in lactating rats through Upregulation of α-Lactalbumin and aquaporin expression.

BACKGROUND: Polyherbal formula (PHF) contains extract of Sauropus androgynous (L.) Merr., Trigonella foenum-graceum L., and Moringa oleifera Lam. considered to induce galactagogue activity. This research aimed to evaluate the galactagogue activity of PHF and its effects on α-lactalbumin (LALBA) as well as aquaporin (AQP) gene expression at messenger ribonucleic acid (mRNA) levels in mammary glands of lactating rats. METHODS: Thirty lactating Wistar rats were randomly divided into five groups (n = 6), each has 7 pups. Group I was treated orally with distilled water as negative control. Groups II, III, and IV were orally administered with PHF at 26.25, 52.5 and 105 mg/kg/day, respectively. Group V was treated with domperidone 2.7 mg/kg/day, orally as positive control. The treatment was performed at third day until fifteenth day of parturition. The observed parameters include the galactagogue activity indicating by milk yield of lactating rats, the pup weight changes and lactating rats body weight changes during lactating period, mRNA expression of LALBA and AQP using quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and histopathological analysis of mammary glands at the end of treatment period. RESULT: The result showed that the PHF groups (52.5 and 105 mg/kg/day) and domperidone were significantly increased milk production of lactating rats (p < 0.05). The levels of mRNA expression of LALBA and AQPs were significantly upregulated by 105 mg/kg/day of PHF or 2.7 mg/kg of domperidone administration (p < 0.0001). Histopathological analysis of mammary glands shows that alveoli diameter was increase 14.59 and 19.33% at 105 mg/kg of PHF and 2.7 mg/kg of domperidone treatment, respectively. CONCLUSION: The study suggested that PHF has potentially to induce galactagogue activity on lactating period through upregulation of LALBA and AQP genes at the mRNA level.