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In pharmaceutical discovery, the "magic methyl" effect describes a substantial improvement in the pharmacological properties of a drug candidate with the incorporation of methyl groups. Therefore, to expedite the synthesis of methylated drug analogs, late-stage, undirected methylations of C(sp3)-H bonds in complex molecules would be valuable. However, current methods for site-selective methylations are limited to activated C(sp3)-H bonds. Here we describe a site-selective, undirected methylation of unactivated C(sp3)-H bonds, enabled by photochemically activated peroxides and a nickel(II) complex whose turnover is enhanced by an ancillary ligand. The methodology displays compatibility with a wide range of functional groups and a high selectivity for tertiary C-H bonds, making it suitable for the late-stage methylation of complex organic compounds that contain multiple alkyl C-H bonds, such as terpene natural products, peptides, and active pharmaceutical ingredients. Overall, this method provides a synthetic tool to explore the "magic methyl" effect in drug discovery.

Herein, we report concise total syntheses of diterpene natural products (-)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. Our synthesis features a convergent Kozikowski β-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2 + 2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5-6-4-5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5-6-4-5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed us to complete total syntheses of (-)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR3-catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.

A simple empirical method is described that allows the assignment of absolute configurations of natural products containing chiral vicinal bromochloro (VBC) units, including the bromochloro substituted isoprenyl units present in the structures of antiproliferative halomon (1a) and its halogen-swapped isomer iso-halomon (1b) from the red alga, Portieria hornemannii, and callophycols A (3) and B (4) from Callophycus serratus. The relative configurations of 3 and 4, published in 2007, were incomplete: C-16 was left unassigned. It is now shown that the additivity of molar rotations, [M]D (herein, abbreviated [M])─a consequence of vant Hoffs principle of optical superposition─could be used to deconvolute rotatory contributions, designated as [MX] and [MY] of the two remotely spaced chiral substructures within 3 and 4 using simple arithmetic. Input of proxy values, [M Y1] and [MY2], for the two different VBC units in two equations for [MX] and application of a conditional test returns the same value for [MX] only when a proxy with the correct configuration is included. It is revealed that 3 and 4 have opposite configurations at the C-16 stereocenter: 16S and 16R, respectively. Two important implications lie in these findings: 3 and 4 appear to qualify as paired-regioisomers, coupled through a putative dyotropic rearrangement (DR), and the biosyntheses of other Callophycus secondary metabolites, now numbering over 50, are tightly controlled by stereoelectronic considerations including neighboring group interactions of the DR. It now appears, counter to earlier suggestions, that the chirality of Callophycus secondary metabolites, despite their high chemodiversity, are surprisingly highly conserved. Enantiofacial halogenation additions to the C═C double bonds of precursor alkenes appear to direct the formation of the remaining stereocenters at both the halogenated benzoate-decalin core and the distal VBC of 3 and 4. A consistent hypothesis is proposed to account for macrolactonizations in other Callophycus natural products including bromophycolides A and B. The conditional test of molar rotations was applied in a different context to understand the chiroptical properties and trends observed in the highly iodinated meroditerpenes, iodocallophycols A-E, also from Callophycus sp., resulting in the revision of the configuration of callophycol E from (10R,14R) to (10S,14S).

Glycosylation is a ubiquitous modification present across all of biology, affecting many things such as physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Nucleotide sugars are important precursors needed to study glycosylation and produce glycosylated products. Saccharomyces cerevisiae is a potentially powerful platform for producing glycosylated biomolecules, but it lacks nucleotide sugar diversity. Nucleotide sugar metabolism is complex, and understanding how to engineer it will be necessary to both access and study heterologous glycosylations found across biology. This review overviews the potential challenges with engineering nucleotide sugar metabolism in yeast from the salvage pathways that convert free sugars to their associated UDP-sugars to de novo synthesis where nucleotide sugars are interconverted through a complex metabolic network with governing feedback mechanisms. Finally, recent examples of engineering complex glycosylation of small molecules in S. cerevisiae are explored and assessed.

Skeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners - representing the reverse of the proposed biosynthesis (i.e., a contra-biosynthesis approach). Computational evaluation of our designed transformation prompted us to investigate a Büchner-Curtius-Schlotterbeck reaction of a p-quinol methylether, which ultimately results in the synthesis of harringtonolide in two steps from cephanolide A, which we had previously prepared. Additional computational studies reveal that unconventional selectivity outcomes are driven by the choice of a Lewis acid and the nucleophile, which should inform further developments of these types of reactions.

Objective: The predictability and long-term success of periodontal regeneration begins with oral hygiene education, disease management, and an individually tailored periodontal maintenance protocol. The treatment outcomes could be enhanced when biologics and bone grafts are combined. The aim of this report was to describe the outcome of two complex infrabony defects in the same patient treated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and freeze-dried bone allograft (FDBA) over 10 years. Case presentation: Two complex infrabony defects were treated following guided tissue regeneration principles and procedures. Fullthickness flaps were raised to allow visualization of the defects. The areas were debrided, and exposed root surfaces were planed. FDBA and rhPDGF-BB were combined to fill both defects. A collagen membrane was used over the bone graft in one case. The flaps were reapproximated to achieve primary closure. The patient was seen for regular periodontal maintenance visits and clinical and radiographic follow-ups over 10 years. Throughout the examination periods, the probing depths improved without bleeding on probing, and there was radiographic evidence of bone regeneration. Conclusion: The growth factorinfused bone graft was successfully utilized for periodontal regeneration in complex bony defects. [ABSTRACT FROM AUTHOR]

UNLABELLED: In an effort to identify novel compounds with potent inhibition against Toxoplasma gondii, a phenotypic screen was performed utilizing a library of 683 pure compounds derived primarily from terrestrial and marine fungi. An initial screen with a fixed concentration of 5 µM yielded 91 hits with inhibition comparable to an equal concentration of artemisinin. These compounds were then triaged based on known biological and chemical concerns and liabilities. From these, 49 prioritized compounds were tested in a dose response format with T. gondii and human foreskin fibroblasts (HFFs) for cytotoxicity. Ten compounds were identified with an IC50 less than 150 nM and a selectivity index (SI) greater than 100. An additional eight compounds demonstrated submicromolar IC50 and SI values equal to or greater than 35. While the majority of these scaffolds have been previously implicated against apicomplexan parasites, their activities in T. gondii were largely unknown. Herein, we report the T. gondii activity of these compounds with chemotypes including xanthoquinodins, peptaibols, heptelidic acid analogs, and fumagillin analogs, with multiple compounds demonstrating exceptional potency in T. gondii and limited toxicity to HFFs at the highest concentrations tested. IMPORTANCE: Current therapeutics for treating toxoplasmosis remain insufficient, demonstrating high cytotoxicity, poor bioavailability, limited efficacy, and drug resistance. Additional research is needed to develop novel compounds with high efficacy and low cytotoxicity. The success of artemisinin and other natural products in treating malaria highlights the potential of natural products as anti-protozoan therapeutics. However, the exploration of natural products in T. gondii drug discovery has been less comprehensive, leaving untapped potential. By leveraging the resources available for the malaria drug discovery campaign, we conducted a phenotypic screen utilizing a set of natural products previously screened against Plasmodium falciparum. Our study revealed 18 compounds with high potency and low cytotoxicity in T. gondii, including four novel scaffolds with no previously reported activity in T. gondii. These new scaffolds may serve as starting points for the development of toxoplasmosis therapeutics but could also serve as tool compounds for target identification studies using chemogenomic approach.

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Many machine learning techniques are used as drug discovery tools with the intent to speed characterization by determining relationships between compound structure and biological function. However, particularly in anticancer drug discovery, these models often make only binary decisions about the biological activity for a narrow scope of drug targets. We present a feed-forward neural network, PECAN (Prediction Engine for the Cytostatic Activity of Natural product-like compounds), that simultaneously classifies the potential antiproliferative activity of compounds against 59 cancer cell lines. It predicts the activity to be one of six categories, indicating not only if activity is present but the degree of activity. Using an independent subset of NCI data as a test set, we show that PECAN can reach 60.1% accuracy in a six-way classification and present further evidence that it classifies based on useful structural features of compounds using a within-one measure that reaches 93.0% accuracy.

BACKGROUND AND AIMS: We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohns disease [CD], focusing on outcomes in the biologic era. METHODS: Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. RESULTS: Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. CONCLUSION: In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.

Marine-derived Streptomyces have long been recognized as a source of novel, pharmaceutically relevant natural products. Among these bacteria, the MAR4 clade within the genus Streptomyces has been identified as metabolically rich, yielding over 93 different compounds to date. MAR4 strains are particularly noteworthy for the production of halogenated hybrid isoprenoid natural products, a relatively rare class of bacterial metabolites that possess a wide range of biological activities. MAR4 genomes are enriched in vanadium haloperoxidase and prenyltransferase genes, thus accounting for the production of these compounds. Functional characterization of the enzymes encoded in MAR4 genomes has advanced our understanding of halogenated, hybrid isoprenoid biosynthesis. Despite the exceptional biosynthetic capabilities of MAR4 bacteria, the large body of research they have stimulated has yet to be compiled. Here we review 35 years of natural product research on MAR4 strains and update the molecular diversity of this unique group of bacteria.

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p

BACKGROUND RESULTS CONCLUSION The potential for the efficient conversion of lignocellulosic biomass has been extensively explored to produce a wide range of bioproducts. Many approaches have been sought for the deep conversion of lignin to generate products that are toxin‐free and beneficial for processing into high‐value‐added components.This study reported a fungus isolated from the deep sea with strong synthesis of multiple lignocellulases, conversion of lignin and guaiacol (0.1%) by 71.6% and 86.1% within 9 days at 30 °C respectively, and outstanding environmental adaptability (20–50 °C and pH 3–8). Metabolic pathway profiling showed that this fungus utilized lignin to rapidly activate multiple ring‐opening reactions including the 2,3‐ and 3,4‐cleavage pathways, with the 2,3‐cleavage pathway predominating after 5 days. Conversion of metabolic intermediates confirmed the superb potential of this strain for lignin treatment. Meanwhile, its shikimic acid pathway was metabolically active under lignin.This further expands the potential to produce valuable bioproducts during lignin treatment, especially under ambient conditions, which can significantly enhance high‐value precursor compound production. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Oxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs. Methods: The predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations. Results: There were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007). Conclusions: An intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA. [ABSTRACT FROM AUTHOR]

Natural products derived from various sources, including plants, have garnered significant interest as alternative therapeutic options. Among these, Tualang honey, extracted from the nectar of Tualang trees (Koompassia excelsa (Becc.) Taub.), has a long history of traditional use due to its therapeutic properties. This review aims to examine the pharmacological activities of Tualang honey, encompassing both in vitro and in vivo studies. A systematic search was conducted in multiple databases, including PubMed, Springer, Scopus, Wiley, and Science Direct, up until December 2022 to identify relevant studies on the pharmacological activities of Tualang honey. Two independent reviewers were involved in article selection, followed by data extraction and assessment of methodological quality using Syrcle's risk of bias tool. 123 articles were included, collectively describing the pharmacological activities of Tualang honey, including antimicrobial, anticancer, anti-inflammatory, antioxidant, antinociceptive, neuroprotective effects, and others. Tualang honey has significant promise as an alternative treatment option for treating a wide range of pathological diseases due to its wide range of pharmacological properties. Tualang honey's diverse array of pharmacological actions indicates its potential for multiple medicinal uses. [ABSTRACT FROM AUTHOR]

Background: Remote sensing based on multispectral imaging may be useful for detecting vegetation stress responses in agriculture. Objectives: To evaluate the potential of orbital multispectral imaging in discriminating the most effective strategies for reducing plant-parasitic nematode populations, thereby preventing yield losses in coffee production. Methods: Coffee plants were treated with eleven treatments, including Bacillus spp. isolates, commercial biological products, commercial chemical nematicides, and water (control group). Initial and final nematode populations in the soil were quantified, and surface reflectance data were collected using the Planet orbital multispectral sensor. The data were classified using the random tree algorithm. Results: The population of plant-parasitic nematodes was reduced by 35.90% and 55.13% following the application of B. amyloliquefaciens isolate B266 and B. subtilis isolate B33, respectively. Under the conditions of this experiment, multispectral imaging accurately discriminated the most nematicidal treatments, with a global accuracy of 80%. Conclusions: Orbital multispectral imaging can discriminate the most effective treatments used for nematode management in coffee plants, highlighting its potential as a supportive tool in agriculture. [ABSTRACT FROM AUTHOR]

In recent decades, considerable advances have been made in assuring the safety of blood transfusion and organ transplantation. However, with the increasing movement of medical products of human origin across international boundaries, there is a need to enhance global norms and governance. These products, which include blood, organs, tissues, cells, human milk and faecal microbiota, are today crucial for health care but they also pose unique risks due to their human origin, such as disease transmission and graft failure. Moreover, the demand for medical products of human origin often exceeds supply, leading to dependence on international supply chains, and emerging technologies like cell and gene therapy present further challenges because of their unproven efficacy and long-term risks. Current regulatory mechanisms, especially in low- and middle-income countries, are insufficient. The World Health Organization (WHO) has both the mandate and experience to lead the development of international quality and safety standards, consistent product nomenclature, and robust traceability and biovigilance systems. An international, multistakeholder approach is critical for addressing the complexities of how medical products of human origin are used globally and for ensuring their safety. This approach will require promoting uniform product descriptions, enhancing digital communication systems and leveraging existing resources to support countries in establishing regulations for these products. As illustrated by World Health Assembly resolution WHA77.4 on transplantation in 2024, WHO's ongoing efforts to ensure the safe, efficient and ethical use of medical products of human origin worldwide provide the opportunity to galvanize international cooperation on establishing norms. [ABSTRACT FROM AUTHOR]

Biotechnology holds the potential to revolutionize textile dyeing by utilizing biopigments, biodegradable dyes, and fermentative dyeing methods as alternatives to synthetic options. While some challenges exist, these biotechnological approaches offer innovative solutions to minimize environmental impact and foster sustainable practices, leading toward a greener, circular and efficient textile bioindustry. [ABSTRACT FROM AUTHOR]

Background and Aims: Regenerative orthopedics involves approaches like stem cell therapy, platelet-rich plasma (PRP) therapy, the use of biological scaffold implants, tissue engineering, etc. We aim to present a scoping review of the role of artificial intelligence (AI) in different treatment approaches of regenerative orthopedics. Methods: Using the PRISMA guidelines, a search for articles for the last ten years (2013–2024) on PubMed was done, using several keywords. We have discussed the state-of-the-art, strengths/benefits, and limitations of the published research, and provide a useful resource for the way ahead in future for researchers working in this area. Results: Using the eligibility criteria out of 82 initially screened publications, we included 18 studies for this review. We noticed that the treatment responses to regenerative treatments depend on several factors; hence, to facilitate better comprehensive and patient-specific treatments, AI technology is very useful. Machine learning (ML) and deep learning (DL) are a few of the most frequently used AI techniques. They use a data-driven approach for training models to make human-like decisions. Data are fed to the ML/DL algorithm and the trained model makes classifications or predictions based on its learning. Conclusion: The area of regenerative orthopedics is highly sophisticated and significantly aids in providing cost-effective and non-invasive treatments to patients suffering from orthopedic ailments and injuries. Due to its promising future, the use of AI in regenerative orthopedics is an emerging and promising research field; however, its universal clinical applications are associated with some ethical considerations, which need addressing. [ABSTRACT FROM AUTHOR]

Three new representatives of the genus Pseudomonas have been identified that are capable of utilizing abscisic acid and positively influencing the growth and development of plants. Their physiological and biochemical properties have been studied. Based on analysis of the 16S rRNA gene, they were identified as P. veronii IB K11-1 (99.86% similarity) and P. frederiksbergensis IB Ta10m (100%), and strain TaE2 was assigned to Pseudomonas sp. It was found that bacteria, when grown on a mineral-salt medium with ABA, reduced the hormone content by 50–60% with an increase in population density by two orders of magnitude. In a laboratory experiment, it was shown that the introduction of the bacterial biomass (108 CFU/g of substrate) into the rhizosphere of wheat plants ten days after treatment led to a decrease in the abscisic acid content in the roots by 18–30% and an increase in plant weight by up to 30%. Thus, new strains of growth-stimulating ABA-degrading bacteria have been identified and characterized for the first time, which may be promising for the creation of biological products that increase plant resistance to biotic and abiotic stresses. [ABSTRACT FROM AUTHOR]

A collection of ring distorted analogue of Nootkatone including 6 CTD (Complex to Diversity) compounds and 9 SAR (Structure Activity Relationship) compounds were synthesized utilizing the carbonyl group as a starting reaction point. [ABSTRACT FROM AUTHOR]

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B. [ABSTRACT FROM AUTHOR]

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Background: Nanostructured materials used have unique properties and many uses in nanotechnology. The most striking of these is using herbal compounds for the green synthesis of nanoparticles. Among the nanoparticle types used for green synthesis, gold nanoparticles (AuNPs) are used for cancer therapy due to their stable structure and non-cytotoxic. Lung cancer is the most common and most dangerous cancer worldwide in terms of survival and prognosis. In this study, Nasturtium officinale (L.) extract (NO), which contains biomolecules with antioxidant and anticancer effects, was used to biosynthesize AuNPs, and after their characterization, the effect of the green-synthesized AuNPs against lung cancer was evaluated in vitro. Methods: Ultraviolet‒visible (UV‒Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), multiple analysis platform (MAP), and Fourier transform infrared (FT-IR) spectroscopy analyses were performed to characterize the AuNPs prepared from the N. officinale plant extract. Moreover, the antioxidant activity, total phenolic and flavonoid contents and DNA interactions were examined. Additionally, A549 lung cancer cells were treated with 2–48 µg/mL Nasturtium officinale gold nanoparticles (NOAuNPs) for 24 and 48 h to determine the effects on cell viability. The toxicity of the synthesized NOAuNPs to lung cancer cells was determined by the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anticancer effect of the NOAuNPs was evaluated by apoptosis and cell cycle analyses using flow cytometry. Results: The average size of the NPs was 56.4 nm. The intensities of the Au peaks from EDS analysis indicated that the AuNPs were synthesized successfully. Moreover, the in vitro antioxidant activities of the NO and NOAuNPs were evaluated; these materials gave values of 31.78 ± 1.71% and 31.62 ± 0.46%, respectively, in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay at 200 g/mL and values of 25.89 ± 1.90% and 33.81 ± 0.62%, respectively, in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The NO and NOAuNPs gave values of 0.389 ± 0.027 and 0.308 ± 0.005, respectively, in the ferrous ion reducing antioxidant capacity (FRAP) assay and values of 0.078 ± 0.009 and 0.172 ± 0.027, respectively, in the copper ion reducing antioxidant capacity (CUPRAC) assay. When the DNA cleavage activities of NO and the NOAuNPs were evaluated via hydrolysis, both samples cleaved DNA starting at a concentration of 25 g/mL in the cell culture analysis, while the nanoformulation of the NO components gave greater therapeutic and anticancer effects. We determined that the Au nanoparticles were not toxic to A549 cells. Moreover, after treatment with the half-maximal inhibitory concentration (IC50), determined by the MTT assay with A549 cells, we found that at 24 and 48 h, while the necrosis rates were high in cells treated with NO, the rates of apoptosis were greater in cells treated with NOAuNPs. Notably, for anticancer treatment, activating apoptotic pathways that do not cause inflammation is preferred. We believe that these results will pave the way for the use of NOAuNPs in in vitro studies of other types of cancer. Conclusion: In this study, AuNPs were successfully synthesized from N. officinale extract. The biosynthesized AuNPs exhibited toxicity to and apoptotic effects on A549 lung cancer cells. Based on these findings, we suggest that green-synthesized AuNPs are promising new therapeutic agents for lung cancer treatment. However, since this was an in vitro study, further research should be performed in in vivo lung cancer models to support our findings and to explain the mechanism of action at the molecular level. [ABSTRACT FROM AUTHOR]

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI. [ABSTRACT FROM AUTHOR]

Bioassays are regulated, analytical methods used to ensure proper activity (potency) of biological products at release and during long-term storage. Potency is commonly reported on a relative basis by comparing and calibrating a concentration–response curve from the test material to that of a reference standard material. The relative potency approach depends on an assumption that the two concentration–response curves exhibit similar (equivalent) shapes, except for a potency shift. In certain circumstances, however, biological factors preclude the similarity assumption, and the traditional approach becomes unworkable. The antibody-mediated cytotoxicity assay is one example where the similarity assumption does not always hold. Other examples also arise in the fields of toxicology and pharmacology. In this work, we present a non-constant mean relative potency approach which averages the relative potency across a common range of the concentration-response curves. The proposed method captures the changing nature of the relative potency into a summary statistic that can be reported for batch calibration and quality control purposes. We provide inferential methods for this statistic and summarize the results of a simulation comparing these methods across a number of non-constant relative potency scenarios and assay conditions. [ABSTRACT FROM AUTHOR]

Objective: Clinical studies have demonstrated the effectiveness of arthrocentesis in managing temporomandibular joint disorders (TMDs). However, there is a lack of consensus among these studies regarding the selection of injectables. Furthermore, an increasing number of drugs have been tested for TMDs in recent years, complicating the decision-making process for clinicians. This study conducted a network meta-analysis of randomized controlled trials (RCTs) to compare the clinical efficacy of different arthrocentesis treatment regimens. Methods: We conducted a comprehensive search of Embase, PubMed, Cochrane Library, and Web of Science to gather articles on RCTs pertaining to the management of TMDs using arthrocentesis. This search spanned from inception of these databases up to July 29, 2024. We then performed a network meta-analysis using Stata 17.0 software. The outcome indicators used were VAS scores and changes in unassisted maximum opening. To determine the efficacy of each regimen, we employed surface-under the cumulative ranking curve (SUCRA) ranking. Result: Forty RCTs were included, encompassing 1904 temporomandibular joints (TMJs) cases. Treatment options encompass platelet-rich plasma (PRP), hyaluronic acid (HA), corticosteroids (CS), bone marrow concentrate (BMAC), injectable platelet-rich fibrin (i-PRF), concentrated growth factor (CGF), Tenoxicam (TX), microfragmented adipose tissue (FAT), and their combination regimens. The SUCRA ranking revealed that the most effective treatment options at 1-, 3-, and 6-months post-arthrocentesis were HA + PRP, i-PRF, and BMAC, respectively. Conclusion: HA + PRP, i-PRF and BMAC may represent the optimal arthrocentesis agents for the management of TMDs symptoms and restoration of TMJ function in the short, medium, and long term, respectively. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024563975. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment options for patients with advanced renal cancer are limited, as one of the main methods, chemotherapy, is prone to drug resistance in the course of treatment. There have been numerous studies confirming that ferroptosis is involved in the development of renal cancer and drug resistance during treatment. In this review, we provide new insights into the resistance of classical chemotherapy drugs sorafenib and sunitinib in renal cancer and explore the mechanism of different types of ferroptosis-related drugs to treat renal cancer, such as herb extract medicine, ferroptosis inducers, natural compounds, nanomaterials, etc. We have also conducted an in-depth discussion on the application of ferroptosis-related drugs in the clinical treatment of renal cancer. Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer. [ABSTRACT FROM AUTHOR]

Cellulosic biomass is the most abundantly available natural carbon-based renewable resource on Earth. Its widespread availability, combined with rising awareness, evolving policies, and changing regulations supporting sustainable practices, has propelled its role as a crucial renewable feedstock to meet the escalating demand for eco-friendly and renewable materials, chemicals, and fuels. Initially, biorefinery models using cellulosic biomass had focused on single-product platform, primarily monomeric sugars for biofuel. However, since the launch of the first pioneering cellulosic plants in 2014, these models have undergone significant revisions to adapt their biomass upgrading strategy. These changes aim to diversify the bioproduct portfolio and improve the revenue streams of cellulosic biomass biorefineries. Within this area of research and development, enzyme-based technologies can play a significant role by contributing to eco-design in producing and creating innovative bioproducts. This Feature Article highlights our strategies and recent progress in utilizing the biological diversity and inherent selectivity of enzymes to develop and continuously optimize sustainable enzyme-based technologies with distinct application approaches. We have advanced technologies for standalone platforms, which produce various forms of cellulose nanomaterials engineered with customized and enhanced properties and high yields. Additionally, we have tailored technologies for integration within a biorefinery concept. This biorefinery approach prioritizes designing tailored processes to establish bionanomaterials, such as cellulose and lignin nanoparticles, and bioactive molecules as part of a new multi-bioproduct platform for cellulosic biomass biorefineries. These innovations expand the range of bioproducts that can be produced from cellulosic biomass, transcending the conventional focus on monomeric sugars for biofuel production to include biomaterials biorefinery. This shift thereby contributes to strengthening the Bioeconomy strategy and supporting the achievement of several Sustainable Development Goals (SDGs) of the 2030 Agenda for Sustainable Development. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in agriculture is a global concern that is growing every day. As a result, there is increasing interest in investigating different approaches to disease control in both plants and animals. Research on the identification and synthesis of antimicrobial compounds derived from plants and microbes has exploded in the last few years. The purpose of this review is to give a broad overview of the current knowledge regarding antimicrobials derived from plants and microbes and their possible uses in agricultural practises. It discusses a number of topics, such as the origins of these antimicrobial agents, how they work, and how well they work to fight infections in plants and animals. Furthermore, the difficulties pertaining to their execution and potential outcomes are examined. [ABSTRACT FROM AUTHOR]

The elimination of residual host cell DNA (HCD) and proteins (HCPs) is a pivotal step in the purification process for biological products such as monoclonal antibodies, recombinant proteins, vaccines, gene therapy vectors, and cell‐based therapies. During the preparation of recombinant staphylokinase (r‐SAK), a potential therapeutic protein for thrombotic disorders expressed in Escherichia coli cells, an efficient chromatography purification process, incorporating anion exchange, cation exchange, and gel filtration techniques, was developed to effectively eliminate HCPs and residual DNA. This multistep chromatography approach yielded r‐SAK with a residual HCD concentration below 1 ng/mL, a residual HCP concentration below 0.01%, and purity exceeding 98%. Comparative analysis revealed that modified cellulose‐based matrix resins exhibited superior efficiency compared to dextran and agarose matrix resins for eliminating residual HCPs and HCD under identical conditions. Based on the different properties of the matrix, deductions were made regarding the reasons for the differentiation in separation efficiency. The physical strength of the cellulose‐based matrix ensures the structural stability of macroporous resin and can guarantee efficient separation under conditions of high flow and heavy load. This study suggests that maintaining the structural stability of macropores in bioseparation materials is crucial for improving the efficiency of separating biological products. [ABSTRACT FROM AUTHOR]

The article provides an overview of the relaunch of the Clinical Trials Information System (CTIS) and the updated transparency rules following the implementation of the EU Clinical Trials Regulation (CTR) in January 2023. It discusses the balance between transparency and protection of commercially confidential information, resulting in the non-publication of certain documents. The article also mentions the CORE Reference Project, which offers resources and professional development for regulatory medical writers. It further highlights selected regulatory information and updates in the field of regulatory public disclosure, including the FDA's transition to the Modernized ClinicalTrials.gov and the WHO's introduction of an online platform for medical device information. Library patrons researching these topics may find the underlying text valuable for further exploration. [Extracted from the article]

Background and Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials. Methods: Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results: The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion: Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase. [ABSTRACT FROM AUTHOR]

IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular weights smaller than 12 kDa and a specific portion of nucleotides. The medical uses of IMUNOR include therapeutic applications within its registered range of indications, primarily for the treatment of immunodeficiencies, allergies, and certain acute or relapsing bacterial infections in adults and children. Despite the long-term clinical application of DLE, with strong evidence of positive therapeutic effects and no serious side effects, a detailed physicochemical specification of this mixture was lacking. We developed several methods for more in-depth physicochemical characterization of IMUNOR, including a spectrophotometric method for quantification of the total protein concentration and total DNA concentration in a mixture, several chromatographic methods for identification of individual components present in significant concentrations in IMUNOR, such as HPLC methods and the Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis method, and characterization of amino acid composition of this mixture. For the investigation of the variability among different batches of IMUNOR, five to nine representative batches from a standard manufacturing process on an industrial scale were utilized. Using the analytical methods, we verified and confirmed the batch-to-batch reproducibility of the biological product IMUNOR. [ABSTRACT FROM AUTHOR]

The production of oak seedlings in intensive crops involves the modification of natural conditions, namely the degree of humidity, through artificial irrigation, which favors the appearance of the pathogen Erysiphe alphitoides, responsible for the Oak Powdery Mildew (OPM) disease. Thus, it is necessary to identify new substances and technologies to control OPM. In this sense, new products approved by the European Union (EU) and Forest Stewardship Council (FSC) were identified, both synthetic and, a great novelty, biological (based on chito-oligosaccharides-oligogalacturonans: COS-OGA). In order to quantify the results, a correlation was made with climatic factors, by sampling data related to temperature and relative humidity with Data Logger devices. The obtained results suggest that OPM has a high virulence in the temperature range of 20 to 30 °C; at a relative humidity above 75%. The data obtained from the field experiments show that the synthetic products controlled OPM with an effectiveness between 70% and 95%, and the biological product behaved almost similarly, between 60% and 90%, which creates high opportunities for environmentally friendly control of forest pathogens. [ABSTRACT FROM AUTHOR]

Feedstock variability represents a challenge in lignocellulosic biorefineries, as it can influence both lignocellulose deconstruction and microbial conversion processes for biofuels and biochemicals production. The impact of feedstock variability on microbial performance remains underexplored, and predictive tools for microbial behaviour are needed to mitigate risks in biorefinery scale‐up. Here, twelve batches of corn stover were deconstructed via deacetylation, mechanical refining, and enzymatic hydrolysis to generate lignin‐rich and sugar streams. These batches and their derived streams were characterised to identify their chemical components, and the streams were used as substrates for producing muconate and butyrate by engineered Pseudomonas putida and wildtype Clostridium tyrobutyricum, respectively. Bacterial performance (growth, product titers, yields, and productivities) differed among the batches, but no strong correlations were identified between feedstock composition and performance. To provide metabolic insights into the origin of these differences, we evaluated the effect of twenty‐three isolated chemical components on these microbes, including three components in relevant bioprocess settings in bioreactors, and we found that growth‐inhibitory concentrations were outside the ranges observed in the streams. Overall, this study generates a foundational dataset on P. putida and C. tyrobutyricum performance to enable future predictive models and underscores their resilience in effectively converting fluctuating lignocellulose‐derived streams into bioproducts. [ABSTRACT FROM AUTHOR]

Chronic repeated-dose toxicity studies are required to support long-term dosing in late-stage clinical trials, providing data to adequately characterize adverse effects of potential concern for human safety. Different regulatory guidances for the design and duration of chronic toxicity studies are available, with flexibility in approaches often adopted for specific drug modalities. These guidances may provide opportunities to reduce time, cost, compound requirement and animal use within drug development programs if applied more broadly and considered outside their current scopes of use. This article summarizes presentations from a workshop at the 43rd Annual Meeting of the American College of Toxicology (ACT) in November 2022, discussing different approaches for chronic toxicity studies. A recent industry collaboration between the Netherlands Medicines Evaluation Board (MEB) and UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) illustrated current practices and the value of chronic toxicity studies for monoclonal antibodies (mAbs) and evaluated a weight of evidence (WOE) model where a 3-month study rather than a 6-month study might be adequate. Other topics included potential opportunities for single-species chronic toxicity studies for small molecules, peptides and oligonucleotides and whether a 6-month duration non-rodent study can be used more routinely than a 9-month study (similar to ICH S6(R1) for biological products). Also addressed were opportunities to optimize recovery animal use if warranted and whether restriction to one study only (if at all) can be applied more widely within and outside ICH S6(R1). [ABSTRACT FROM AUTHOR]

Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC. [ABSTRACT FROM AUTHOR]

Still's disease (SD) is a rare systemic inflammatory disease that is characterized by high fever, polyarthritis, and an evanescent rash as its main symptoms but that may also be complicated by pleuritis and macrophage activation syndrome (MAS). There has been a recent increase in studies on older-onset SD, which presents with less-typical clinical features, such as sore throat, skin lesions, and splenomegaly, but more complications including pleuritis and disseminated intravascular coagulation. Several reports have shown higher levels of inflammatory markers, including serum ferritin, and poorer outcomes in terms of survival and drug-free remission in older patients. In addition, caution is needed when diagnosing SD in older patients because of the increased incidence of differential diagnoses such as infectious diseases, malignancies, and inflammatory diseases. Prognosis is poor in older patients, and treatment-associated infections and severe complications such as MAS are the main cause of mortality. The use of biologics and treatment response may not differ greatly between older and younger patients. Although the data are limited, anti-IL-1 and anti-IL-6 agents may control SD in these patients with careful use and adequate infection prevention. Recent studies that classified adult-onset SD by cluster analysis or latent class analysis showed that older patients form a unique cluster of SD, indicating the need for clinicians to pay more attention to the diagnosis and management of SD in older patients. [ABSTRACT FROM AUTHOR]

Glycan profile comparisons are one of the most tedious analytical exercises for establishing compliance with recombinant therapeutic protein batches. Based on its intensive research, the FDA has confirmed that lectin array binding with fluorescent monitoring is the fastest and most reliable method for profile comparisons. Using a database of over 150 biological products expressed in nine diverse mammalian cell systems, the FDA immobilized 74 lectins to study their binding using fluorescently labeled glycoproteins. The FDA identified nine distinct lectins from a custom-designed lectin microarray: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHALs, which detect core fucose, terminal GlcNAc, terminal β-galactose, high mannose, α-2,3-linked sialic acids, α-2,6-linked sialic acids, bisecting GlcNAc, terminal α-galactose, and triantennary structures, respectively. This method can be used for screening and routine testing and to monitor batch-to-batch variability of therapeutic proteins, including establishing analytical similarity as a crucial part of biosimilar development. [ABSTRACT FROM AUTHOR]

This article provides an overview of the FDA's efforts to promote diversity in clinical trials. The FDA has released guidance documents since 2016 to encourage the inclusion of diverse populations in trials. The article emphasizes the importance of inclusive criteria and discusses the potential of decentralized trials and digital health technology to increase diversity. The FDA recommends self-reporting of race and ethnicity information and expects to release further guidance in the future. Sponsors are advised to comply with these recommendations and be prepared for future diversity action plans. [Extracted from the article]

Simple Summary: Head and Neck Cancer is often diagnosed at an advanced stage, resulting in poor long-term prognosis. Additionally, this cancer is resistant to chemotherapy. This systematic review article aims to examine the literature on published methods to overcome resistance to chemotherapy for head and neck cancer. According to the "cancer stem cell" (CSCs) theory, tumors are a diverse and expanding group of malignant cells that originate from a small number of CSCs. Despite treatment, these cells can still become active and proliferate, which can result in distant metastasis and local recurrences. A new paradigm in cancer treatment involves targeting both CSCs and the cancer cells in a tumor. This review aims to examine the literature on methods published to overcome chemoresistance due to the presence of CSCs in head and neck cancers. The review was registered with PROSPERO (ID# CRD42024512809). After Pub Med, Scopus, and WoS database searches, 31 relevant articles on oral squamous cell carcinoma (OSCC) were selected. Compounds that increased chemosensitivity by targeting CSCs in head and neck squamous cell carcinoma (HNSCC) were divided into (1) natural products, (2) adjuvant molecules to traditional chemotherapy, and (3) CSCs targeting patient-specific fresh biopsies for functional precision medicine. [ABSTRACT FROM AUTHOR]

Objectives Autoreactive memory B cells (MBCs) contribute to chronic and progressive courses in autoimmune diseases like SLE. The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and LN, is generally attributed to depletion of activated naïve B cells and inhibition of B-cell activation. BEL's effect on MBCs is currently unexplained. We performed an in-depth cellular and transcriptomic analysis of BEL's impact on the blood MBC compartment in patients with SLE. Methods A retrospective meta-analysis was conducted, pooling flow cytometry data from four randomized trials involving 1245 patients with SLE treated with intravenous BEL or placebo. Then, extensive MBC phenotyping was performed using high-sensitivity flow cytometry in patients with mild/moderate SLE and severe SLE/LN treated with subcutaneous BEL. Finally, transcriptomic characterization of surging MBCs was performed by single-cell RNA sequencing. Results In BEL-treated patients, a significant increase in circulating MBCs, in a broad range of MBC subsets, was established at week 2, gradually returning to baseline by week 52. The increase was most prominent in patients with higher SLE disease activity, serologically active patients and patients aged ≤18 years. MBCs had a non-proliferating phenotype with a prominent decrease in activation status and downregulation of numerous migration genes. Conclusion Upon BEL initiation, an increase of MBCs was firmly established. In the small cohort investigated, circulating MBCs were de-activated, non-proliferative and demonstrated characteristics of disrupted lymphocyte trafficking, expanding on our understanding of the therapeutic mechanism of B-cell-activating factor inhibition by BEL. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT00071487, NCT00410384, NCT01632241, NCT01649765, NCT03312907, NCT03747159. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta‐analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. Materials and methods: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta‐analysis. Results: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3–1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667–1.360; p = 0.789; I2 = 73.271) efficacy. Conclusions: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times. [ABSTRACT FROM AUTHOR]

Bamboo, recognized for its rapid growth, high yield, and fiber performance is prominent in the fiber‐based bioproduct industry. However, the absence of US industrial bamboo plantations for fiber production necessitates reliance on imports or locally manufactured products using imported bamboo fibers, predominantly from China. This study evaluates the economic viability of cultivating bamboo in the Southern US for fiber production, with a case study on hygiene tissue products. The supply‐chain analysis was assessed to calculate bamboo chips' minimum selling price (MSP) at the farm gate for an 8% internal rate of return (IRR). The MSP, influenced primarily by land rental costs, ranges from USD 48 to 55 per bone‐dry metric ton (BDt). Despite an initial establishment cost of ~USD 2 000 ha−1 and profitability by year 5, bamboo is a viable, long‐term fiber alternative. Successful bamboo cultivation in the US could lead to a more sustainable implementation of alternative non‐wood fibers for hygiene tissue applications. [ABSTRACT FROM AUTHOR]

In the evolving field of bioproducts, materials that synergize sustainability with functionality are of paramount importance. Mycelium composites, derived from intricate networks of fungal filaments, are gaining traction as innovative bioproducts that offer a compelling blend of eco‐friendliness, renewability, and adaptability. As the quest intensifies for alternatives that can mitigate the environmental toll of conventional products, mycelium‐based solutions are emerging as beacons on the sustainable bioproducts horizon. Their transition from niche innovations to mainstream applications depends on their ability to overcome a series of fabrication challenges. This review paper investigates the critical challenges faced in the fabrication of mycelium composite. It examines rigorously some essential factors leading to fabrication failure, such as contamination, inconsistent growth, insufficient moisture, inappropriate pH, and improper substrate preparation. The review offers a comprehensive analysis of each factor influencing mycelium growth and the resulting composite properties, with an emphasis on preventative and mitigating strategies. Through an in‐depth exploration of case studies detailing unsuccessful mycelium composite fabrication, the significance of understanding these failure factors is emphasized. The paper culminates in a forward‐thinking discourse on potential strategies for refining fabrication processes, and identifies promising research areas poised to enhance both the success rate and overall efficiency of mycelium composite production. [ABSTRACT FROM AUTHOR]

The article examines the relationship between biologic treatments for psoriasis and the risk of developing depression, based on a retrospective analysis of U.S. administrative claims data. Topics include the reduced incidence of depression among patients using biologics compared to conventional treatments, the relative risk reduction associated with different classes of biologics, and the implications of these findings for future treatment strategies.

The role of buffer in modulating the enzymatic hydrolysis environment of lignocellulose is crucial. However, studies on the impact of buffer on high-solid enzymatic hydrolysis remain limited. This study discovered that utilizing deionized water as a reaction medium, rather than the conventional buffer, did not influence the enzymatic hydrolysis of steam-exploded corn stover when the solid loading ranged between 15 and 25%. At 15% solid loading, the glucan conversion in the group treated with buffer was recorded at 89.8%, with a corresponding glucose concentration of 51.1 g/L. In contrast, the group without buffer exhibited a conversion of 88.9% and a glucose concentration of 50.5 g/L. The increase of acid groups in lignin was attributed to the formation of phenolic hydroxyls during steam explosion, which provided the substrate with the necessary conditions for buffering effects. Sequentially, during the high-solid enzymatic hydrolysis process, the substrate's increased pore volume and specific surface area could potentially offset the buffering capacity, which led to the buffering effect becoming ineffective. Leveraging the self-buffering effect of the substrate, a fed-batch strategy was developed. This strategy replaced the water supplementation with buffers, augmenting the solid loading from 20 to 33% across six distinct feeding sessions over a span of 72 h. This not only reduced costs but also laid the foundation for the industrial viability of lignocellulosic high-concentration sugar production, thereby advancing the biofuels and bioproducts sector. These findings provide valuable insights for the exploration of solid reaction processes. [ABSTRACT FROM AUTHOR]

The main objective of this study was to develop a citric acid-catalyzed hydrothermal pretreatment to reach the maximum sugar recovery from soybean hull (SH), in the context of a biorefi nery concept. A central composite design (CCD) was used to optimize pretreatment conditions through the analysis of citric acid concentration, time, and temperature effects. Optimized conditions were defined as 3.56% w/w, 46.1 min, and 135.7 °C. From the solid fraction, 99.5% and 83.0% of glucose and xylose conversion, respectively, were obtained after enzymatic hydrolysis. Sugars were fermented successfully to L-lactic acid by Lactobacillus pentosus. In fact, SH hydrolysate presented no trace of inhibitor compounds, and glucose was totally consumed during fermentation. After 24 h of fermentation, a conversion rate of 0.724 g/g of sugars to lactic acid and 80.5% of the stoichiometric theoretical yield were reached. In addition, from the liquid fraction, 47.8 mg/g of xylooligosaccharides (XOS) was produced. This work demonstrates the potential of SH to be exploited as feedstock, with mild and efficient pretreatment process, for medium- to high-value bioproducts production in biorefineries. [ABSTRACT FROM AUTHOR]