D-Glucosamine is a Potential Urease Inhibitor from Middle Eastern Medicinal Plants for Combatting Helicobacter Pylori Infections; a Molecular Docking and Simulation Approach.

Helicobacter pylori stands as a significant risk factor for both peptic and stomach ulcers. Their resistance to the highly acidic host environment primarily stems from their capability to produce urease, an enzyme that rapidly converts urea into NH3 and CO2. These byproducts are crucial for the bacterium's survival under such harsh conditions. Given the pivotal role of medicinal plants in treating various ailments with minimal side effects, there is an urgent need for a natural drug that can effectively eliminate H. pylori by inhibiting urease. Hence, the current study aims to identify the most potent urease inhibitor among the natural compounds found in Middle Eastern medicinal plants, taking into consideration factors such as optimal affinity, drug-like properties, pharmacokinetic characteristics, and thermodynamic attributes. In total, 5599 ligand conformers from 151 medicinal plants were subjected to docking against the urease's active site. The top-ranking natural compounds, as determined by their high docking scores, were selected for further analysis. Among these compounds, D-glucosamine (PubChem code 439,213) exhibited the most interactions with the crucial amino acid residues in the urease's active site. Furthermore, D-glucosamine demonstrated superior absorption, distribution, metabolism, excretion, and toxicity properties compared to other top-ranked candidates. Molecular dynamics simulations conducted over 100 nanoseconds revealed stable root mean square deviations and fluctuations of the protein upon complexation with D-glucosamine. Additionally, the radius of gyration and solvent-accessible surface area values for the D-glucosamine-urease complex were notably lower than those observed in other typical urease-inhibitor complexes. In conclusion, this study provides valuable insights into the potential development of D-glucosamine as a novel urease inhibitor. This promising compound holds the potential to serve as an effective drug for combating H. pylori infections in the near future.

Assessing Therapeutic Value and Side Effects of Key Botanical Compounds for Optimized Medical Treatments.

Due to the significance of variable chemical groups across a wide spectrum of modern medicine, it is imperative to determine what is the most widely used group in medical applications with the fewest side effects. Ten compounds from ten chemical groups that are most commonly known for their medical uses were compared in terms of their therapeutic potential and side effects. The comparison among the selected compounds indicated the superiority of the flavonoids over other groups in the multitude of their utilizations and the lower side effects. Kaempferol and quercetin showed higher medical utilization with lower side effects. Whereas alkaloid compounds showed the lowest levels of medical use and the highest levels of side effects. Based on the comparison conducted, it is concluded to give priority to flavonoid compounds being used in medical applications because they exhibit the highest medical uses with the lowest side effects. Within flavonoids, kaempferol and quercetin are the two compounds that are highly recommended to be used in the widest range of medical applications. Serious caution should be considered before applying alkaloids to any medical service. Understanding the characteristics of these compounds can aid in developing safer and more effective treatments for medicinal plants.

The emergence of novel Iranian variants in sheeppox and goatpox viral envelope proteins with remarkably altered putative binding affinities with the host receptor.

The outbreak of Sheep and goat pox (SGP) viral infections have increasingly been reported despite vaccinating the majority of sheep populations in Iran. The objective of this study was to predict the impacts of the SGP P32/envelope variations on the binding with host receptors as a candidate tool to assess this outbreak. The targeted gene was amplified in a total of 101 viral samples, and the PCR products were subjected to Sanger sequencing. The polymorphism and phylogenetic interactions of the identified variants were assessed. Molecular docking was performed between the identified P32 variants and the host receptor and the effects of these variants were evaluated. Eighteen variations were identified in the investigated P32 gene with variable silent and missense effects on the envelope protein. Five groups (G1-G5) of amino acid variations were identified. While there were no amino acid variations in the G1 (wild-type) viral protein, G2, G3, G4, and G5 proteins had seven, nine, twelve, and fourteen SNPs, respectively. Based on the observed amino acid substitutions, multiple distinct phylogenetic places were occupied from the identified viral groups. Dramatic alterations were identified between G2, G4, and G5 variants with their proteoglycan receptor, while the highest binding was revealed between goatpox G5 variant with the same receptor. It was suggested that the higher severity of goatpox viral infection originated from its higher affinity to bind with its cognate receptor. This firm binding may be explained by the observed higher severity of the SGP cases from which G5 samples were isolated.

An efficient, fast and inexpensive method for genomic DNA extraction of fish tissue.

BACKGROUND: DNA extraction is an essential step for many genetic techniques like PCR and other molecular analyses. Based on the method of extraction and type of tissue used, the quality of extracted DNA for genetic studies varies. An appropriate extraction method is evaluated by the high concentration and purity of DNA. Thus, this study aimed to find a more efficient and effective method of DNA extraction from fish tissues and compare it to commercially available kits. METHODS AND RESULTS: A total of 200 fish tissue samples were extracted using each method and then validated with restriction enzymes and PCR amplification. The result revealed that the mean quantity of the isolated genomic DNA, when measured by Nanodrop for grass and common carp, was estimated at (624.41 ± 34.51) µg/ml and (651.27 ± 46.31) µg/ml, respectively, and the purity of this DNA was about (1.83 ± 0.04) and (1.88 ± 0.03) respectively, as compared to commercial extraction kits. Furthermore, gel electrophoresis was performed on the PCR-ready DNA, and the results were confirmed with restriction enzymes and PCR amplification. Based on results obtained from restriction enzymes and PCR analysis, it was determined that no significant inhibitors existed for the enzymes that were used in molecular biology reactions. CONCLUSION: As a result, this technique provides an efficient and versatile alternative to the traditional method for obtaining bulk amounts of highly qualified DNA from fish tissue and can be easily used for subsequent analyses such as PCR and several molecular experiments on other fish species.

The relationship between OXT gene polymorphisms and reproductive hormones in pregnant and lactating Awassi Ewes.

BACKGROUND: Numerous genetic loci interact intricately to control reproduction in mammals. The oxytocin gene (OXT) is a promising candidate for reproductive traits in mammals. Previously, sheep and goats have been studied for the presence of the OXT polymorphism. As of yet, no polymorphisms have been identified in the OXT gene of Awassi sheep. Thus, this study was conducted to determine the effects of OXT polymorphism and litter size on reproductive hormones in pregnant and lactating Awassi ewes. METHODS AND RESULTS: This study evaluated 232 ewes aged 3 and 4 years (123 single-progeny ewes and 109 twin-producing ewes). Serum was collected to measure reproductive hormones using ELISA kits manufactured by ELK Biotechnology. DNA was extracted from sheep blood for genotyping and sequencing to identify variations in OXT gene (exon 2, 266 bp). Genotyping analysis revealed three genotypes within 266 bp: CC, CA, and AA. Sequence analysis revealed a novel mutation in exon 2: 188 C > A. Statistical analysis showed significant associations between the 188 C > A SNP and phenotypic traits. Twin-pregnant ewes carrying CC genotypes had higher estrogen, progesterone, and follicle-stimulating hormone/luteinizing hormone levels (65.86 ± 3.87) (pg/mL), (6.51 ± 0.39) (ng/mL), and (20.22 ± 1.27) (ng/mL)/( 23.37 ± 2.14) (ng/mL) respectively, compared to CA and AA genotypes in the fourth month of twin-pregnant ewes compared to single-pregnant ewes. CONCLUSIONS: This study found that the 188 C > A SNP negatively affected reproductive hormone levels in Awassi sheep. These findings provide breeders with a new insight into the sheep OXT gene, useful for future breeding.

A Novel Missense SNP in the Fatty Acid-Binding Protein 4 (FABP4) Gene is Associated with Growth Traits in Karakul and Awassi Sheep.

The fatty acid-binding protein 4 (FABP4) plays a crucial role in the transportation and metabolism of fatty acids. It binds to long-chain fatty acids and facilitates their transport within cells. FABP4 is involved in lipid metabolism, insulin sensitivity, inflammation, and energy homeostasis. This study was conducted to assess the association between the FABP4 gene and growth traits in Karakul and Awassi sheep. A PCR-single strand conformation polymorphism (SSCP) protocol was utilized to assess the polymorphism of FABP4 PCR products with growth traits measured at birth, three, six, nine, and twelve-month intervals. One non-synonymous SNP was identified in the second exon, in which threonine was converted to aspartate in the 61st position in FABP4 (p.61Thr > Asp). This novel SNP showed significant associations with all growth traits measured at all age intervals. The results showed that lambs with the TT genotype exhibited higher growth traits than those with the GT and GG genotypes, respectively. The conducted prediction showed a clearly deleterious effect of p.61Thr > Asp on FABP4 structure, which was accompanied by reduced fatty acid binding efficiency. Owing to the predicted damaging effects caused by p.61Thr > Asp on FABP, lower levels of lipid transport and its consequent increased weight gain and other growth trait indices are expected. Therefore, a putative mechanism through which lambs with these genotypes exhibit higher growth traits is proposed. The FABP4 gene is suggested as a promising marker to improve growth traits in Karakul and Awassi sheep. However, more research is required to validate this mechanism.

A missense SNP in the proopiomelanocortin (POMC) gene is associated with growth traits in Awassi and Karakul sheep.

This study was conducted to assess the association between proopiomelanocortin (POMC) gene and growth traits in Awassi and Karakul sheep. PCR-single strand conformation polymorphism (SSCP) method was utilized to assess the polymorphism of POMC PCR amplicons with body weight and length, wither and rump height, chest and abdominal circumference measured at birth, 3, 6, 9, and 12 months intervals. Only one missense SNP (rs424417456:C > A) was detected in exon-2, in which glycine was converted to cysteine in the 65th position in POMC (p.65Gly > Cys). rs424417456 SNP showed significant associations with all growth traits in the third, sixth, ninth, and twelfth months. At the age of 3 months onward, lambs with CC genotype showed higher body weight, body length, wither and rump heights, and chest and abdominal circumferences than lambs with CA and AA genotypes, respectively. Prediction analyses indicated a deleterious effect of p.65Gly > Cys on POMC structure, function, and stability. Owing to the strong correlation between rs424417456:CC and better growth characteristics, this genotype is proposed as a promising marker to enhance growth traits in Awassi and Karakul sheep. The predicted damaging effects caused by rs424417456:CA and rs424417456:AA genotypes may entail a putative mechanism through which lambs with these genotypes exhibit lower growth traits.

The identification of a novel SNP in the resistin (RETN) gene associated with growth traits in Karakul and Awassi sheep.

Resistin is one of the most important adipocytokines in mammalian cells due to its involvement in insulin resistance, obesity, and autoimmune diseases. Resistin is encoded by RETN gene that is primarily expressed in adipose tissues. Mutations in this gene have been associated with several productive traits in animals. This study was conducted to assess the possible biomarker capacity of RETN by evaluating its association with growth traits in two economically important sheep in the Middle East. Genotyping was conducted using PCR-single strand conformation polymorphism (SSCP), and the polymorphism of RETN was associated with several growth traits for three months intervals starting from birth until one year of age. In a total of 190 Karakul sheep and 245 Awassi sheep, only one SNP (233A > C) was detected in the RETN gene. The identified novel SNP showed significant associations with all growth traits at the ages of six, nine, and twelve months. At the age of six months onward, lambs with AC and CC genotypes showed respectively lower body weight and length, chest and abdominal circumferences, and wither and rump heights than those with AA genotype. Due to the remarkable association between RETN;233A > C and lower growth traits, this genotype is suggested as a promising marker to assess growth traits in Karakul and Awassi sheep. This is the first study that demonstrated the importance of RETN as a possible tool for evaluating growth traits in two breeds of sheep with a possibility to be applied to other breeds via large-scale association analysis.

Two missense variants of the epidermal growth factor receptor gene are associated with non small cell lung carcinoma in the subjects from Iraq.

BACKGROUND: Lung carcinoma is a foremost cause of cancer-related mortality worldwide. Variable genetic factors are associated with the development of lung cancer. This study was performed to evaluate the possible association of epidermal growth factor receptor (EGFR) gene polymorphisms with non small cell lung carcinoma (NSCLC) in Iraqi population. METHODS: DNA samples were extracted from 100 patients and 100 controls. Four PCR fragments were designed to amplify four high-frequency variants within EGFR, namely rs1050171, rs2072454, rs2227984, and rs2227983. The PCR fragments were genotyped by single-strand conformation polymorphism (SSCP) method, and each genotype was subjected to direct sequencing. RESULTS: Genotyping experiments confirmed the variability of three targeted variants, and logistic regression analysis showed that two of these variants (rs1050171 and rs2227983) tend to exhibit a significant association with NSCLC. Individuals with rs1050171:GA genotype showed a possible association with the increased risk of NSCLC (P = 0.0110; OD 5.2636; Cl95% 1.4630 to 18.9371). Individuals with rs2227983:GG genotype exhibited a potential association with NSCLC (P = 0.0037; OD 5.2683; Cl95% 1.7141 to 16.1919). Linkage disequilibrium analysis showed that the effects of the investigated variants seem to take independent actions, and no haplotype was found to be associated with the high prevalence of NSCLC. CONCLUSIONS: Our collective data indicated that EGFR-rs1050171G/A and EGFR-rs2227983G/G SNPs tend to exert significant and separate associations with the increased risk of NSCLC. However, this study recommends using a broader spectrum of the investigated samples to get further details of both SNPs in terms of their association with the susceptibility to NSCLC.

Phylogenetic differentiation between Awassi and Hamdani sheep using the mitochondrial 12S rRNA.

This study was conducted to assess the role of the mitochondrial 12S rRNA variations in the phylogenetic discrimination between two Iraqi breeds of sheep that differ in geographical distribution. A total of 122 animals (68 Awassi and 54 Hamdani) were included in the study. Direct sequencing of amplicons followed by the construction of a median-joining network and several trees were performed to identify the possible phylogenetic differences between both involved breeds. Genetic diversity, relative frequencies, and analysis of molecular variance (AMOVA) were performed to assess the genetic correlation between both populations. The median-joining network and minimized tree values showed that all observed haplotypes were separated into two groups according to their breed. Comprehensive phylogenetic data revealed only one Asian ancestor for all observed haplotypes. As indicated by AMOVA, the observed diversity was mostly due to between-population variation (1.24836%), while within-population variation (0.91221%) accounted for much less. The currently investigated rRNA amplicons exhibited different mitochondrial manifestations between Awassi and Hamdani breeds. Due to the ability of these 12S rRNA amplicons to mimic the geographical diversity for the currently investigated breeds, it is highly recommended to be used as potent mitochondrial genetic markers among broader ovine sequences.

A novel deleterious oxytocin variant is associated with the lower twinning ratio in Awassi ewes.

This study aimed to assess the possible association of oxytocin (OXT) gene with reproductive traits in two groups of Awassi ewes that differ in their reproductive potentials. Sheep were genotyped using PCR-single-stranded conformation polymorphism approach. Three genotypes were detected in exon 2, CC, CA, and AA, and a novel SNP was identified with a missense effect on oxytocin (c.188C > A → p.Arg55Leu). A significant (p < 0.01) association of p.Arg55Leu with the twinning rate was found as ewes with AA and CA genotypes exhibited, respectively a lower twinning ratio than those with the wild-type CC genotype. The deleterious impact of p.Arg55Leu was demonstrated by all in silico tools that were utilized to assess the effect of this variant on the structure, function, and stability of oxytocin. Molecular docking showed that p.Arg55Leu caused a dramatic alteration in the binding of oxytocin with its receptor and reduced the number of interacted amino acids between them. Our study suggests that ewes with AA and CA genotypes showed a lower reproductive performance due to the presence of p.Arg55Leu, which caused damaging impacts on oxytocin and is binding with the OXT receptor. The utilization of the p.Arg55Leu could be useful for improving Awassi reproductive potential.

Deleterious missense variants in the aflatoxin biosynthesis genes explain the low toxicity of Aspergillus flavus from infected rice.

Aspergillus flavus is one of the most natural contaminants of the improperly stored rice grains. It produces several secondary metabolites, like aflatoxins, which are well known hepatotoxic, hepatocarcinogenic and mutagenic agents. This study describes the in silico consequences of the missense mutations identified in several genes of aflatoxins biosynthesis in rice-contaminating A. flavus isolates. In the in vitro portion of the study, aflatoxins production profile was measured, and PCR-single strand-conformation polymorphism (SSCP)-sequencing method was used to genotype the studied genetic loci: aflP, aflM, aflR, PEP, and cob. Results showed aflatoxigenic potential in 79 out of 109 A. flavus isolates. Twenty-two missense and fifty-five synonymous mutations were found to be distributed variably on the studied loci. In the in silico portion of this study, several computations were utilized to predict the effect of each observed missense mutation on proteins structure, function, and stability. Seven mutations (O-methyl transferase: p.G256C; ver-1 dehydrogenase: p.K179 N and p.V183L; aspergillopepsin-1: p.P137L, p.S138F, p.G154C, and p.S158C) were found to be highly deleterious among the missense variants with damaging effects on their proteins' structure and function. In contrast to these detected variations in the aflatoxigenic loci, all missense mutations in the control non-aflatoxigenic cob gene were found to be neutral. These findings indicated that the observed mutations may reduce the concomitant biohazard of their biosynthesized aflatoxins. The current findings suggest that the naturally available variants may reduce or eliminates the dangerous consequences of aflatoxins upon ingesting the rice infected with A. flavus. To the best of our knowledge, this study is the first comprehensive report to analyze the missense mutations on the aflatoxin biosynthesis genes using in vitro and the state-of-art bio-computational tools.

A Novel Missense Single Nucleotide Polymorphism in the GREM1 Gene is Highly Associated with Higher Reproductive Traits in Awassi Sheep.

GREM1 (gremlin1) is a known inhibitor for BMP15 (bone morphogenetic protein 15) family, but its genetic diversity in sheep is unknown. The present study was conducted to analyze the polymorphism of GREM1 gene using PCR- single-strand conformation polymorphism (SSCP) and DNA sequencing methods and to assess the possible association of GREM1 gene polymorphism with reproductive traits in Awassi ewes. A total of 224 ewes, 124 producing singles and 100 producing twins, were included in the study. Two SSCP patterns were detected in two amplified loci within the exon 2. Two exonic novel single nucleotide polymorphism (SNP)s were identified, c.74 T > G (the silent SNP p.Met123 =) and c.30 T > A with (the missense SNP p.Ile237Phe). Statistical analyses indicated a non-significant (P > 0.05) association of p.Met123 = with the analyzed reproductive traits of fecundity, prolificacy, litter size, and twinning rate. Meanwhile, p.Ile237Phe SNP exhibited a highly significant (P < 0.01) association with the measured reproductive traits, in which ewes with TA genotype (with p.Ile237Phe SNP) exhibited higher litter size, twinning ratio, fecundity, and prolificacy than those with TT genotype (without p.Ile237Phe SNP). The deleterious impact of p.Ile237Phe SNP was observed by the means of ten different state-of-the-art in silico tools that predicted a highly damaging effect of p.Ile237Phe SNP on the structure, function, and stability of gremlin1. In conclusion, the results of our study suggest that p.Ile237Phe SNP has a remarkable negative impact on the gremlin1 structure, function, and stability. Since gremlin1 is a known inhibitor of reproductive performance, a consequent higher reproductive performance was observed in ewes with damaged gremlin1 (with p.Ile237Phe SNP) than those with non-damaged gremlin1 (without p.Ile237Phe SNP). Therefore, it can be stated that the implementation of the novel p.Ile237Phe SNP in the GREM1 gene could be a useful marker in marker-assisted selection. This manuscript is the first one to describe GREM1 gene variations in sheep.

A computational approach for explaining the effect of the prl gene polymorphism on prolactin structure and biological activity in Japanese quails.

Prolactin is a versatile hormone with multiple activities, including a negative control on egg production. This study was conducted to genotype all the coding portions of the prl gene using PCR-SSCP-sequencing, and to investigate the effects of amino acid substitutions of the prl gene on the structure and function of prolactin in quails using in silico approach. Though all genotyped exons exerted homogenous PCR-SSCP patterns, a total of 12 novel SNPs were detected in the investigated exons, including three SNPs in exon-1, 8 SNPs in exon-2, and one SNP in exon-4. Three adjacent missense SNPs were detected in exon-2, namely H69P, T70P, and S71F. Computational tools indicated obvious deleterious effects of T70P, with less extent to H69P and S71F on prolactin functions and activity, which may lead to limited participation of this hormone in the negative control of egg production. In conclusion, the introduction of in silico prediction has suggested an alternative solution for the breeders to evaluate the effect of each witnessed nsSNP in protein structure and function. The current study suggests three nsSNPs, T70P, T70P, and S71F as strong candidates for the negative effect on prolactin biological activity with a consequent reversal positive effect on egg productivity traits.

A novel T177P missense variant in the HSPA8 gene associated with the low tolerance of Awassi sheep to heat stress.

This study was conducted to identify the association of coding variations in the HSPA8 gene with heat stress in two different breeds of sheep. All the coding regions of the HSPA8 gene of Awassi and Arabi sheep were covered by amplifying nine exons. A single-strand conformation polymorphism (SSCP) was utilized to assess the genetic variations in both breeds. The possible association of the observed genotypes with rectal temperature (RT), respiratory rate (RR), and heat tolerance coefficient (HTC) was analyzed in different seasons. While all the coding regions of both sheep were monomorphous, a remarkable heterogeneity was observed in exon 4, of which two SSCP patterns, a normal TT and a mutant TG, were detected. The TG genotype was characterized by a missense variant of T177P with frequencies of 77% in Awassi and 54% in Arabi. Cumulative in silico tools indicated extremely deleterious consequences for T177P on protein structure, function, and stability. Results indicated that sheep with the TT genotype had significantly (P < 0.05) lower RT, RR, and HTC values than sheep with the TG genotype. Therefore, a significant association of T177P with a lower tolerance of Awassi to higher temperature conditions was revealed. In conclusion, the identified T177P may have damaging effects in the HSPA8, which affects the ability of Awassi sheep to cope up with elevated temperatures compared with Arabi sheep. This manuscript describes a novel description of a highly deleterious missense variant in the HSPA8 gene that may reduce the ability of sheep to withstand high-temperature conditions.

Co-inherited novel SNPs of the LIPE gene associated with increased carcass dressing and decreased fat-tail weight in Awassi breed.

The lipase E hormone-sensitive (LIPE) enzyme is one of the lipolytic enzymes, and it plays a key role in the regulation of adipose tissue deposition. This study was conducted to investigate the possible association between the LIPE gene variations and the main body weight measurements in Awassi sheep. A total of 160 of sexually mature Awassi rams (Ovis aries) that aged between 2 and 3 years were included in the present study. Genomic DNA was extracted and two specific PCR amplicons were designed to amplify two coding regions within the LIPE gene. Genotyping experiments were performed using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP). Two different SSCP banding patterns were identified, CC and CD in exon 2, and AA and AT in exon 9. Five novel single-nucleotide polymorphisms (SNPs) were detected by sequencing, namely g.151C > A and g.198C > T in exon 2, and g.213G > C, g.226G > T, and g.232A > C in exon 9. Haplotype block analysis showed strong linkage disequilibrium values between the two SNPs in exon 2 and the three SNPs in exon 9. Association analysis of haplotypes with carcass traits demonstrated a significantly higher dressing percentage (P < 0.05) and lower fat tail weight (FTW) in CACT and GCGTAC haplotypes made these haplotypes more favorable for human consumption. The current research is the first one to report a tight association between the LIPE genetic polymorphism and the dressing percentage and FTW traits, suggesting a pivotal role played by these co-inherited SNPs in the metabolism of carcass traits in sheep.

Optimal pcr primers for rapid and accurate detection of Aspergillus flavus isolates.

Aspergillus flavus is among the most devastating opportunistic pathogens of several food crops including rice, due to its high production of carcinogenic aflatoxins. The presence of these organisms in economically important rice strip farming is a serious food safety concern. Several polymerase chain reaction (PCR) primers have been designed to detect this species; however, a comparative assessment of their accuracy has not been conducted. This study aims to identify the optimal diagnostic PCR primers for the identification of A. flavus, among widely available primers. We isolated 122 A. flavus native isolates from randomly collected rice strips (N = 300). We identified 109 isolates to the genus level using universal fungal PCR primer pairs. Nine pairs of primers were examined for their PCR diagnostic specificity on the 109 isolates. FLA PCR was found to be the optimal PCR primer pair for specific identification of the native isolates, over aflP(1), aflM, aflA, aflD, aflP(3), aflP(2), and aflR. The PEP primer pair was found to be the most unsuitable for A. flavus identification. In conclusion, the present study indicates the powerful specificity of the FLA PCR primer over other commonly available diagnostic primers for accurate, rapid, and large-scale identification of A. flavus native isolates. This study provides the first simple, practical comparative guide to PCR-based screening of A. flavus infection in rice strips.

Phytochemistry, pharmacology, and medical uses of Oldenlandia (family Rubaceae): a review.

The Oldenlandia genus comprises approximately 240 species of plants, yet only a limited number of these have been investigated for their chemical composition and medicinal properties. These species contain a wide range of compounds such as iridoids, anthraquinones, triterpenes, phytosterols, flavonoids, anthocyanidins, vitamins, essential oils, phenolic acids, and coumarins. These diverse phytochemical profiles underscore the pharmacological potential of Oldenlandia plants for various medical purposes. Among other chemical constituents, ursolic acid stands out as the most important active compound in Oldenlandia, owing to its proven anticancer, anti-inflammatory, antimicrobial, and hepatoprotective properties. The evaluation of Oldenlandia's pharmacological prospects indicates that the holistic utilization of the entire plant yields the most significant effects. Oldenlandia diffusa showcases anticancer and anti-inflammatory capabilities attributed to its varying constituents. Across a broad spectrum of pharmacological capacities, anticancer research predominates, constituting the majority of medical uses. Oldenlandia diffusa emerges as a standout for its remarkable anticancer effects against diverse malignancies. Antioxidant applications follow, with O. corymbosa demonstrating potent antioxidant properties alongside O. umbellata and O. diffusa. Subsequent priority lies in anti-inflammatory studies, wherein O. diffusa exhibits noteworthy efficacy, trailed by O. corymbosa also takes the lead in antimicrobial activity, with O. umbellata as a strong contender. Additional investigation is essential to ascertain the relative significance of these species in various pharmacological applications. This comprehensive assessment underscores the multifaceted potential of Oldenlandia as a versatile herbal resource, offering diverse pharmacological capacities. The call for sustained exploration and research remains essential to unlock the full extent of Oldenlandia's medicinal benefits.

A novel p.127Val>Ile SNP in the MTNR1A gene and its relation to litter size in Thin-tailed Indonesian ewes.

Objective: The primary objective is to identify and characterize the Single Nucleotide Polymorphisms (SNPs) within the MTNR1A gene sequence in thin-tailed Indonesian ewes to assess the possible association of MTNR1A gene polymorphism with litter size trait. Methods: Forty-seven thin-tailed Indonesian sheep were selected for the study. Genotyping involved collecting blood samples, and sequencing exon 2 of the MTNR1A gene. Results: The study identified 19 novel SNPs, with 10 being non-synonymous variations, in the MTNR1A gene of Thin-tailed Indonesian ewes. One non-synonymous SNP (rs1087815963) showed a significant association with litter size, with the GC genotype exhibiting a higher average litter size than the GG genotype. The deleterious impact of p.Val127Ile SNP was predicted by various in silico tools that predicted a highly damaging effect of p.Val127Ile SNP on the structure, function, and stability of MTNR1A. Docking reactions showed a critical involvement of this locus with the binding with melatonin. Conclusion: In conclusion, the results of our study suggest that rs1087815963 has a remarkable negative impact on the MTNR1A with a putative alteration in the binding with melatonin. Therefore, it can be stated that the implementation of the novel p.Val127Ile could be a useful marker in marker-assisted selection.

Targeting Monkeypox Virus Methyltransferase: Virtual Screening of Natural Compounds from Middle-Eastern Medicinal Plants.

Monkeypox is an infectious disease resulting from the monkeypox virus, and its fatality rate varies depending on the virus clade and the location of the outbreak. In monkeypox virus, methyltransferase (MTase) plays a crucial role in modifying the cap structure of viral mRNA. This alteration assists the virus in evading the host's immune system, enhances viral protein synthesis, and ultimately enables successful infection and replication within host cells. Given the significance of MTase in viral infection and spread within the host, our study aimed to identify a natural inhibitor for this enzyme using docking and molecular dynamic (MD) simulations. We collected a total of 12,971 natural compounds from 200 medicinal plants in the Middle East. After eliminating duplicate compounds, we had 5,749 unique ligand conformers, which we then subjected to high-throughput virtual screening against MTase. The most promising hits were further evaluated using the extra-precision (XP) tool. The affinity of these hits was also assessed by Prime-Molecular Mechanics/Generalized Born Surface Area (MMGBSA) tool. The analysis revealed that two standard controls (sinefungin and TO1119) and two Middle-Eastern compounds (folic acid and 1,2,4,6-tetragalloylglucose) exhibited the best XP docking scores. According to Prime MMGBSA calculations, the Middle-Eastern compounds showed higher affinities, with values of - 60.61 kcal/mol for 1,2,4,6-tetragalloylglucose and - 51.87 kcal/mol for folic acid, surpassing the controls (TO1119 at - 35.71 kcal/mol and sinefungin at - 31.51 kcal/mol). In the majority of Molecular dynamic (MD) simulations, folic acid exhibited demonstrated greater stability than sinefungin. Further investigation revealed that folic acid occupied a critical position in the active site of MTase, which reduced its interaction with the mRNA substrate. Based on these findings, it can be concluded that folic acid is a highly promising natural compound for potential use in the cost-effective treatment of monkeypox virus. The identification of folic acid as a potential antiviral agent highlights the importance of nature in providing new therapeutic uses that have significant implications for global health, particularly in regions where monkeypox viral outbreaks are prevalent. However, it is essential to note that further wet-lab validations are necessary to confirm its efficacy for treatment in a medical context.