Acetic Acid Derivatives Research Articles

Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study

BackgroundMetabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited.MethodsTwo-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies.ResultsAll the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases.ConclusionsBy integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

Rational design and synthesis of novel N-benzylindole-based epalrestat analogs as selective aldose reductase inhibitors: An unexpected discovery of a new glucose-lowering agent (AK-4) acting as a mitochondrial uncoupler

Diabetes mellitus is one of the most frequent metabolic diseases associated with hyperglycemia. Although antidiabetic drugs reduce hyperglycemia, diabetic patients suffer from abnormal fluctuations in blood glucose levels leading to the onset of long-term complications. Aldose reductase inhibitors are considered a promising strategy for regulating the occurrence of diabetic-specific comorbidities. So far, epalrestat is the only drug being approved in Asian countries. In this paper, we ground our research in discovering novel epalrestat analogs that prevent chronic complications and normalize hyperglycemia. Herein, we describe the rational design and synthesis of four novel 4-thiazolidinone acetic acid derivatives (AK-1-4) being evaluated for their efficacy against aldose reductase from rat lenses and their specificity over the homologous enzyme from rat kidneys. AK-1-4 were also tested against human recombinant protein tyrosine phosphatase 1B as a key target in insulin sensitization and towards the closely related T-cell-derived enzyme. Docking analyses suggested possible binding modes on examined targets. The promising inhibitory profile of AK-4 sparked our interest in exploring its effect on the insulin-receptor signaling pathway and its ability to stimulate glucose uptake under ex vivo conditions. We further investigated the ability of AK-4 to target mitochondria acting as an uncoupling agent and impairing mitochondrial membrane potential. Herein, we report for the first time a new glucose-lowering agent (AK-4) that can combine alleviation for chronic diabetic complications without off-target adverse effects and antihyperglycemic efficacy through controlled mitochondrial uncoupling activity. Pharmacokinetic and toxicity studies in silico revealed optimal properties of AK-4 for oral administration without potential side effects.

Computational Docking studies of Phenyl Acetic Acid Derivatives with Biological Targets, DNA, Protein and Enzyme

Phenyl acetic acid (PAA) is a well-known biomolecule used in antibiotics and drugs. To elucidate the binding modes of PAA and its derivatives with DNA, Pim kinase protein, and urease enzymes, molecular docking studies were conducted. The results revealed that PAA and its derivatives intercalate with DNA, disrupting its structure and potentially affecting replication, transcription, and repair processes. The 3-chloro-PAA showed the highest docking score (-7.809) and significant polar interactions with DNA residues. For Pim kinase, the compounds exhibited polar interactions with key residues, with 2-propyl PAA demonstrating notable inhibitory effects. Similarly, PAA derivatives interacted effectively with urease enzymes, with the 4-propyl-PAA showing a strong docking score (-8.5250). Overall, the meta-substituted PAAs exhibited superior binding interactions compared to ortho and para-substituted derivatives, suggesting their potential as effective inhibitors for these biological targets.

Isolation and Characterization of Arsenic-Tolerable Bacteria from Groundwater and Their Implementation on Rice Seedling's Shoot and Root Enhancement.

Arsenic exerts detrimental impacts on primary metabolism in plants, leading to reduced crop yield. Some arsenic-resistant plant growth-promoting bacteria (PGPB) help plants by providing some plant hormones to sustain their growth and development under arsenic stress. Here, seven different species of Bacillus were isolated from arsenic-contaminated groundwater of West Bengal, India. Those species were capable of growing in the presence of > 3.12g/L arsenate (AsV) and > 0.65g/L arsenite (AsIII) salts and also resist different heavy metals like Cu2+, Fe2+, Co2+, Zn2+, Pb2+, etc. They were susceptible to multiple groups of antibiotics like beta-lactam, aminoglycosides, etc. All species were capable of detoxifying arsenite and influenced rice seedlings' growth in the presence of arsenic salts by their capabilities likenitrogen-fixing ability, phosphate solubilization, indole 3-acetic acid (IAA), gibberellic acid (GA), proline production, etc. Most species helped enhance root and shoot lengths under arsenic stress. These primary findings suggest that those Bacillus spp. could be used as potential bio-fertilizers in arsenic-contaminated agricultural fields.

Design, Synthesis, Computational Study, and Antidiabetic Evaluation of Benzoxazole Derivatives

AbstractAlpha‐amylase plays a crucial role in blood glucose levels, and thus, its inhibitor can be used to control diabetes. Thus, in vitro alpha‐amylase inhibitory activities were studied for synthesized benzoxazole compounds. The 2‐amino‐benzoxazoles were prepared by reacting 2‐aminophenol with cyanogen bromide, which was coupled with phenoxy acetic acid derivatives (6 a‐n). The compound 6 h was found to be significantly active with IC50 values of 348.43 μg/mL against alpha‐amylase compared to acarbose (IC50=682.54 μg/mL). The molecular docking and molecular dynamic simulation showed better affinity and stability of 6 h at the binding site of the alpha‐amylase protein. Further, a preliminary bioevalauation and antidiabetic study were done through in vivo using SD rats. The efficacy study showed a significant improvement in glucose levels, total cholesterol, triglyceride, LDL, and HDL levels in the compound 6 h and was found to be a lead antidiabetic agent.

Steroidal Anti-Inflammatory Drugs for Oral Surgery: A Systematic Review and Meta-Analysis.

The aim of the present study was to investigate if there are differences in mitigation acute pain following oral surgery procedures within a hospital setting and regarding various medication regimens. A systematic literature search was performed between the years 2013 and 2023, including the databases PUBMED, Cochrane and Scopus, to identify the clinical trials investigating the prescription of non-steroidal (NSAID's) anti-inflammatory drugs before or after an oral surgery. A meta-analysis with meta-regression model was employed on the primary and secondary outcomes, such as pain, swelling and trismus. Thirty-six articles were included, 6 of them being retrospective and 30 prospective, with a higher proportion of women than men, at a ratio of 1.34:1 and an average age of 31.9 years. Drugs with medium duration of action demonstrated lower values for pain and swelling. Regarding these parameters, pain and swelling, propionic acid derivatives and acetic acid derivatives exhibited lower values respectively. The quality of evidence was low to very low- certainty. The meta-analysis suggests that postoperative pain, swelling and trismus following oral surgery management may be effectively treated with the following drugs: NSAID medium-duration action drugs; propionic acid derivatives for lower pain levels and acetic acid derivatives for lower swelling measures; and Ibuprofen 400mg every 8h for 3 days or less. Anti-inflammatory and analgesic drugs are prescribed to prevent or treat dental pain. Ibuprofen 400mg was the most prescribed drug after or before an oral surgery procedure. However, the evidence is indirect and needs to be interpreted with caution.

Acid Strength Effects on Dimerization during Metal-Free Catalytic Dioxygen Reduction.

Development of earth-abundant catalysts for the reduction of dioxygen (ORR) is essential for the development of alternative industrial processes and energy sources. Here, we report a transition metal-free dicationic organocatalyst (Ph2Phen2+) for the ORR. The ORR performance of this compound was studied in acetonitrile solution under both electrochemical conditions and spectrochemical conditions, using halogenated acetic acid derivatives spanning a pKa range of 12.65 to 20.3. Interestingly, it was found that under electrochemical conditions, a kinetically relevant peroxo dimer species forms with all acids. However, under spectrochemical conditions, strong acids diminish the kinetic contribution of this dimer to the observed rate due to lower catalyst concentrations, whereas weaker acids were still rate-limited by the dimer equilibrium. Together, these results provide insight into the mechanisms of ORR by organic-based, metal-free catalysts, suggesting that balancing redox activity and unsaturated character of these molecules with respect to the pKa of intermediates can enable reaction tuning analogous to transition metal-based systems.

NSAIDs, analgesics, antiplatelet drugs, and decline in renal function: a retrospective case-control study with SIDIAP database

IntroductionWe aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR).MethodsWe performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010–2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88–0.97), SYSADOA (0.87;0.83–0.91) and acetaminophen (0.84;0.79–0.89), and an high risk for metamizole (1.07;1.03–1.12), and antiplatelet drugs (1.07;1.03–1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88–0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03–1.15) and Coxibs (1.19;1.08–1.30). Medium and high use of major opioids shows a high risk (1.15;1.03–1.29). Triflusal showed high risk at medium (1.23;1.02–1.48) and high use (1.68;1.40–2.01).ConclusionWe observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results.

In-vitro Regeneration of An Endangered Medicinal Plant Anodendron paniculatum (Apocynaceae)

Objectives: The present study aims to establish a standardized and efficient regeneration protocol for Anodendron paniculatum A. DC. (Apocynaceae) by optimizing the effect of various plant growth regulators as it is categorized globally as an endangered medicinal plant. Methods: MS medium fortified with 3% sucrose (w/v) and different concentrations of cytokinins 6-benzylamino purine (BAP), kinetin, thidiazuron either alone or in combination with auxins, indole 3-acetic acid (IAA), naphthalene acetic acid (NAA) and GA3. For the in vitro root induction, individual and healthy shoots (3-4 cm in length) were excised in the 7th week and were cultured onto basal and half-strength MS medium supplemented with various concentrations of auxins and incubated in the culture room. Findings: MS medium supplemented with thidiazuron (2.5 𝜇M) in combination with indole 3-acetic acid (2.5 𝜇M) and GA3 (1.25 𝜇M) was most effective, providing multiple shoot regeneration for 79.33% of cotyledonary leaf explants associated with a high number of shoots per explant (20.00 ± 1.15) and length of shoot (2.66 ± 0.08 cm). Whereas, the frequency of response, mean number of shoots, and respective lengths were varied with different concentrations of 6-benzylamino purine when used in combination with IAA or NAA and BAP (5.0 𝜇M) along with IAA (2.5 𝜇M) at the frequency of 47.66%. Whereas, the addition of GA3 (1.25 𝜇M) in combination with BAP (5.0 𝜇M) and IAA (2.5 𝜇M) has shown a maximum number of multiple shoot formation/explant (12.33) with length of shoot (1.53 ± 0.08 cm). MS medium supplemented with 10 𝜇M 6-benzyl amino purine and 2.5 𝜇M naphthalene acetic acid recorded the highest response (53.66%) with more number of the shoot (9.66) and length of the shoot (1.83 ± 0.03 cm) per explant. The maximum percentage of response (84.33%) was recorded at 1 2 strength MS medium with 5.0 𝜇M NAA, whereas the highest number of roots per shoot (6.66 ± 0.33) was induced at MS + 5.0 𝜇M NAA. The highest length of roots (3.66 cm) was recorded at basal MS medium fortified with 5.0 𝜇M NAA and 7.5 𝜇M NAA. Novelty: The standardized protocol method is of first of its kind, a quick and suitable approach for the high quantity production of Anodendron paniculatum with appropriate concentrations of plant growth regulators that meet thecommercial demand of endangered medicinal plants. Keywords: Anodendron paniculatum; Endangered plant; Plant growth regulators; Regeneration; Protocol standardization

(5-Oxooxazolidin-4-yl)acetic Acid Derivatives as a Protection for the α-Carboxyl Group of Aspartic Acid: A Word of Caution

(5-Oxooxazolidin-4-yl)acetic Acid Derivatives as a Protection for the α-Carboxyl Group of Aspartic Acid: A Word of Caution

Computer aided design, synthesis and characterisation of thiazolidinedione acetic acid derivatives as brest- cancer inhibitors

The development of new anti-cancer drugs is a dynamic process that is continuously fueled, at the basic level, by the identification of new molecular targets for chemotherapeutic intervention, and, at the clinical level, by the problems (i.e. adherence, tolerability, toxicity, and virus-drug resistance) encountered with existing drugs. Thiazolidin-2,4-dione acetic acids are a class of heterocyclic compounds which possess the aforementioned pharmacophoric features. Thus several benzylidene-thiazolidin-2,4-dione compounds were designed. A total number of 12 compounds were synthesized successfully with good purity. The structures of these compounds have been confirmed by IR &amp; Mass spectrometry. In-vitro studies of the synthesized compounds are yet to be performed &amp; it is expected that these studies will reflect the effectiveness of these molecules as barest cancer inhibitors and will open a new dimension for the synthesis of novel anti-cancer agents. The labile structure of the synthesized compounds allows the possibility of elaborating the present work by increasing the number of derivatives &amp; by altering the positions of substitutions on the root nucleus followed by SAR &amp; QSAR studies. Moreover, compounds of similar nature can be designed which will lead to the synthesis of many more structural analogues.

Effectiveness of Nanoformulated Plant Growth Regulators in the Production and Propagation of High-value Crops and Ornamentals

Among the major classes of plant hormones, auxins, gibberellins, and cytokinins are widely used for plant propagation. These hormones influence the physiological and developmental processes of plants such as root initiation, apical dominance, seed germination, leaf expansion, and development of buds, flowers, and fruits. Its exogenous application was found to significantly improve the growth of several important plants. This study aimed to determine the effectiveness of plant growth regulators (PGRs) derived from naturally occurring plant growth-promoting bacteria (PGPBs) in the production and propagation of selected crops. In this study, indole- 3-acetic acid (IAA) and gibberellic acid (GA) were extracted from naturally occurring PGPB Bacillus sp. The extracted hormone was nanoformulated for controlled release and increased uptake in plants. The nanoformulated hormones were applied in the propagation of coffee and the production of eggplant and ornamentals. Results showed that the application of nanoformulated IAA (Nano-IAA) significantly increased the survival rate of coffee compared to the commercially available auxin. Nano-IAA increased the germination rate of eggplant in acidic soil and root emergence of Bougainvillea over the negative control (water) but was comparable to that of the commercially available auxin. The nanoformulated GAs and commercially available

Diversity of actinomycetes on plant rhizosphere of karst ecosystem of Gorontalo, Indonesia

Abstract. Retnowati Y, Kandowangko NY, Katili AS, Pembengo W. 2024. Diversity of actinomycetes on plant rhizosphere of karst ecosystem of Gorontalo, Indonesia. Biodiversitas 25: 907-915. The objective of this study was to isolate and identify the actinomycetes associated with the rhizosphere of plants in the karst ecosystem. This study was descriptive-quantitative. Soil sampling was conducted at three locations of the karst ecosystem of Gorontalo, i.e., Bangga Hills at Bangga Bubaa Coastal area of Gorontalo District, Hills around Lake Limboto of Gorontalo District, and Oluhuta Beach Hills at Bone Bolango District. Rhizosphere-soil sample was collected from 15-30 cm of soil depth. Isolation of actinomycetes was performed using the plate method. The screening of phosphate-solubilizing bacteria was based on the ability to solubilize phosphates indicated by the clear zone on the Pikovskaya medium. Identification of actinomycetes bacteria based on morphology and molecular characters. The morphology character included the color of aerial and substrate mycelium. Molecular characteristics based on the sequence of 16S rRNA gene compared to sequence data on the gene bank of NCBI. The phylogenetic tree reconstruction was based on the Neighbor-joining algorithm. The results successfully found six isolates, including three actinomycetes isolates, two non-actinomycetes bacteria, and one yeast. They were isolated from the rhizosphere of Malastoma malabathrum, Chromolaena odorata, Cycas rumphii, Leucaena leucocephala, and Jatropha curcas. The actinomycetes isolate showed plant-growth-promoting potential indicated by solubilizing phosphate and Indole 3-Acetic Acid production activities. Based on the molecular analysis, actinomycetes were closely related to Streptomyces aegyptia (MT505707.1:42-1426), Streptomyces sp. GGCR-6 (MH718844.1:5-1391), and Streptomyces carpaticus strain PES-A23 (MH712039).

Design, Synthesis, and Biological Evaluation of Novel Phenoxy Acetic Acid Derivatives as Selective COX-2 Inhibitors Coupled with Comprehensive Bio-Pharmacological Inquiry, Histopathological Profiling, and Toxicological Scrutiny.

COX-2 plays a key role in converting arachidonic acid into prostaglandins. This makes it a significant target for treating inflammation. Selective COX-2 inhibitors have marked a new phase in inflammatory treatment, providing significant effectiveness while reducing negative side effects. Herein, we aimed at the design and synthesis of new anti-inflammatory agents 5a-f, 7a-b, 10a-f, and 13a-b with expected selective inhibition for COX-2. Compounds 5d-f, 7b, and 10c-f showed significant COX-2 inhibition with IC50 in the range of 0.06-0.09 μM, indicating powerful pharmacological potential. In light of this, eight compounds were selected for further testing in vivo to assess their selectivity toward COX-1/COX-2 enzymes with the ability to reduce paw thickness. Compounds 5f and 7b showed significant anti-inflammatory effects without causing stomach ulcers, as they showed significant in vivo inhibition for paw thickness at 63.35% and 46.51%, as well as paw weight at 68.26% and 64.84%. Additionally, the tested compounds lowered TNF-α by 61.04% and 64.88%, as well as PGE-2 by 60.58% and 57.07%, respectively. Furthermore, these potent compounds were thoroughly analyzed for their pain-relieving effects, histological changes, and toxicological properties. Assessing renal and stomach function, as well as measuring liver enzymes AST and ALT, together with kidney indicators creatinine and urea, offered valuable information on their safety profiles. Molecular modeling studies explain the complex ways in which the strong interacts with the COX-2 enzyme. This comprehensive strategy emphasizes the therapeutic potential and safety profiling of these new analogues for managing inflammation.

Physiology and transcriptome of Sapindus mukorossi seeds at different germination stages

Sapindus mukorossi has a wide distribution range, high application value, and broad developmental potential. Previous studies have mostly focused on the medicinal and economic value of soapberry; however, few studies have been conducted on its seed germination. This study measured the physiological indicators and hormone content of soapberry seeds at different germination stages and preliminarily determined that abscisic acid (ABA) and indole-3-acetic acid (IAA) are the key hormones that affect the germination of soapberry seeds. Both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment) analyses detected hormone transduction pathways, further confirming the key role of plant hormones in the germination process of soapberry seeds. Through transcriptome analysis, we speculated that CYP707A and IPA are key genes in the ABA and IAA synthesis pathways, respectively. This study revealed the close relationship between plant hormones and soapberry seed germination and provided new ideas for further exploration of the germination mechanism of soapberry seeds.

Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations.

To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI. In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort. Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac. Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.

Can a Small Change in the Heterocyclic Substituent Significantly Impact the Physicochemical and Biological Properties of (Z)-2-(5-Benzylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic Acid Derivatives?

Rhodanine-3-acetic acid derivatives are attractive compounds with versatile effects. What is very important is that compounds of this type have many biological properties. They are tested, among others, as fluorescent probes for bioimaging and aldose reductase inhibitors. Rhodanine-3-acetic acid derivatives also have antibacterial, antifungal and anticancer activity. The presented work demonstrates that a slight change in the five-membered heterocyclic substituent significantly affects the properties of the compounds under consideration. Three rhodanine-3-acetic acid derivatives (A-1-A-3) were obtained in the Knoevenagel condensation reaction with good yields, ranging from 54% to 71%. High thermal stability of the tested compounds was also demonstrated above 240 °C. The absorption and emission maxima in polar and non-polar solvents were determined. Then, the possibility of using the considered derivatives for fluorescence bioimaging was checked. Compounds A-1 and A-2 were successfully used as fluorescent dyes of fixed cells of mammalian origin. In addition, biological activity tests against bacteria and fungi were carried out. Our results showed that A-1 and A-2 showed the most excellent antimicrobial activity among the newly synthesized compounds, especially against Gram-positive bacteria.

In Vitro Medium-Term Storage of Banana Cultivar ‘Barangan’ Using Alginate-Encapsulation Technique

In vitro medium-term storage using the alginate-encapsulation technique is essential for conserving plant genetic resources, preserving vegetatively propagated species by controlling the growth and development of explants, and maintaining plant biodiversity. The study aimed to obtain the optimum combination medium for the encapsulation of bananas and evaluate the viability of the alginate-encapsulated explants after storage. In vitro, medium- term storage of nodule-like meristem of banana cultivar ‘Barangan’ was performed using sodium alginate, paclobutrazol (PBZ), and Murashige and Skoog (MS) salt. This research consists of 3 stages: (1) Initiation and multiplication of in vitro shoots and nodule-like meristems; (2) In vitro medium-term storage of banana by encapsulation technique; (3) Regeneration of nodule-like meristem explants after in vitro storage. This research showed that the banana's number of nodule-like meristem was optimum on media supplemented with thidiazuron (TDZ) 0.22 mgL-1 and indole 3-acetic acid (IAA) 1.75 mgL-1. Encapsulation explant of nodules-like meristems using 3% sodium alginate in full and half-strength MS salt medium supplemented with PBZ 2.5 mgL-1 and incubated in liquid MS medium was able to store nodule-like meristem for six months. The color of the explants remains green, and the capsule is not damaged. Sub-culture of nodule-like meristem after storage in MS salt medium containing TDZ 0.22 mgL-1 and IAA 1.75 mgL-1 showed that nodules-like meristems could regenerate to form new shoots and nodule-like meristem three months after sub-cultured. This research concludes that encapsulated nodule-like meristem was recorded until six months of storage. PBZ was a necessary retardant in minimizing the growth during storage.

Discovery and optimization of (2-naphthylthio)acetic acid derivative as selective Bfl-1 inhibitor

Bcl-2 anti-apoptotic protein family suppresses cell death by deploying a surface groove to capture the critical BH3 α-helix of pro-apoptotic members. Bfl-1 is a relatively understudied member of this family, though it has been implicated in the pathogenesis and chemoresistance of a variety of human cancers. Reported small molecular Bfl-1 inhibitors encountered the issue of either lack in potency or poor selectivity against its most homologous member Mcl-1. In order to tackle this issue, compound library was screened and a hit compound UMI-77 was identified. We modified its chemical structure to remove the characteristic of PAINS (pan-assay interference compounds), demonstrated the real binding affinity and achieved selectivity against Mcl-1 under the guidance of computational modeling. After optimization 15 was obtained as leading compound to block Bfl-1/BIM interaction in vitro with more than 10-fold selectivity over Mcl-1. We believe 15 is of great value for the exploration of Bfl-1 biological function and its potential as therapeutic target.

Applying Machine Learning and Statistical Forecasting Methods for Enhancing Pharmaceutical Sales Predictions

In today’s evolving global world, the pharmaceutical sector faces an emerging challenge, which is the rapid surge of the global population and the consequent growth in drug production demands. Recognizing this, our study explores the urgent need to strengthen pharmaceutical production capacities, ensuring drugs are allocated and stored strategically to meet diverse regional and demographic needs. Summarizing our key findings, our research focuses on the promising area of drug demand forecasting using artificial intelligence (AI) and machine learning (ML) techniques to enhance predictions in the pharmaceutical field. Supplied with a rich dataset from Kaggle spanning 600,000 sales records from a singular pharmacy, our study embarks on a thorough exploration of univariate time series analysis. Here, we pair conventional analytical tools such as ARIMA with advanced methodologies like LSTM neural networks, all with a singular vision: refining the precision of our sales. Venturing deeper, our data underwent categorisation and were segmented into eight clusters premised on the ATC Anatomical Therapeutic Chemical (ATC) Classification System framework. This segmentation unravels the evident influence of seasonality on drug sales. The analysis not only highlights the effectiveness of machine learning models but also illuminates the remarkable success of XGBoost. This algorithm outperformed traditional models, achieving the lowest MAPE values: 17.89% for M01AB (anti-inflammatory and antirheumatic products, non-steroids, acetic acid derivatives, and related substances), 16.92% for M01AE (anti-inflammatory and antirheumatic products, non-steroids, and propionic acid derivatives), 17.98% for N02BA (analgesics, antipyretics, and anilides), and 16.05% for N02BE (analgesics, antipyretics, pyrazolones, and anilides). XGBoost further demonstrated exceptional precision with the lowest MSE scores: 28.8 for M01AB, 1518.56 for N02BE, and 350.84 for N05C (hypnotics and sedatives). Additionally, the Seasonal Naïve model recorded an MSE of 49.19 for M01AE, while the Single Exponential Smoothing model showed an MSE of 7.19 for N05B. These findings underscore the strengths derived from employing a diverse range of approaches within the forecasting series. In summary, our research accentuates the significance of leveraging machine learning techniques to derive valuable insights for pharmaceutical companies. By applying the power of these methods, companies can optimize their production, storage, distribution, and marketing practices.