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Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.

Atherosclerosis (AS) is the formation of atherosclerotic plaques on the walls of the arteries, causing them to narrow. If this occurs in the coronary arteries, the blood vessels may be completely blocked, resulting in myocardial infarction; if it occurs in the blood vessels of the brain, the blood vessels may be blocked, resulting in cerebral infarction, i.e., stroke. Studies have shown that the pathogenesis of atherosclerosis involves the processes of inflammation, lipid infiltration, oxidative stress, and endothelial damage, etc. SIRT, as a key factor regulating the molecular mechanisms of oxidative stress, inflammation, and aging, has an important impact on the pathogenesis of plaque formation, progression, and vulnerability. Statistics show that AS accounts for about 50 per cent of deaths in Western countries. Currently, oral medication is the mainstay of AS treatment, but its development is limited by side effects, low bioavailability and other unfavourable factors. In recent years, with the rapid development of nano-preparations, researchers have combined statins and natural product drugs within nanopreparations to improve their bioavailability. Based on this, this paper summarises the main pathogenesis of AS and also proposes new oral nanoformulations such as liposomes, nanoparticles, nanoemulsions, and nanocapsules to improve their application in the treatment of AS.

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

The process of synthesizing radionuclide-coupled drugs, especially shutdown technology that links bipotent chelators with biomolecules, utilizes traditional coupling reactions, including emerging click chemistry; these reactions involve different drawbacks, such as complex and cumbersome reaction steps, long reaction times, and the use of catalysts at various pH values, which can negatively impact the effects of the chelating agent. To address the above problems in this study, This research designed a novel bipotent chelator coupled with peptides. In the present study, dichloromethane was used as a solvent, and the reaction was conducted at room temperature for 12 h. A one-step ring-opening method was employed to introduce the coupling functional group of tridentate amide acid. The coupling materials consisted of the amino active site of the peptide and diethylene glycol anhydride. In this paper, this study explored the reactions between different equivalents of acid anhydride coupled to the peptide (peptide sequence: HLRKLRKR) and determined that the maximum conversion of the peptide feedstock was 87%. To determine the selectivity of the reaction sites in this polypeptide, This study identified the peptide sequence at the reaction site using nuclear magnetic resonance (NMR) and liquid chromatography–mass spectrometry (LC-MS). For the selected peptide, the first reactive site was on the terminal amino group, followed by the amino group on the tetra- and hepta-lysine side chains. The tridentate amic acid framework functions as a chelating agent, capable of binding a range of lanthanide ions. This significantly reduces and optimizes the time and cost associated with synthesizing radionuclide-coupled drugs.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.

Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate is the only drug approved by the Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in the search for new compounds or drugs to prevent or cure age-, noise-, or drug-induced hearing loss. Sirtuins are proteins involved in metabolic regulation with the potential to ameliorate sensorineural hearing loss. The mammalian sirtuin family includes seven members, SIRT1-7. This paper is a literature review on the sirtuins and their protective roles in sensorineural hearing loss. Literature search on the NCBI PubMed database and NUsearch included the keywords ‘sirtuin’ and ‘hearing’. Studies on sirtuins without relevance to hearing and studies on hearing without relevance to sirtuins were excluded. Only primary research articles with data on sirtuin expression and physiologic auditory tests were considered. The literature review identified 183 records on sirtuins and hearing. After removing duplicates, eighty-one records remained. After screening for eligibility criteria, there were forty-eight primary research articles with statistically significant data relevant to sirtuins and hearing. Overall, SIRT1 (n = 29) was the most studied sirtuin paralog. Over the last two decades, research on sirtuins and hearing has largely focused on age-, noise-, and drug-induced hearing loss. Past and current studies highlight the role of sirtuins as a mediator of redox homeostasis. However, more studies need to be conducted on the involvement of SIRT2 and SIRT4-7 in hearing protection.

Rarely has a chemical elicited as much controversy as dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product, then a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects on experimental animals. These publications showed contradictory results in vivo and in vitro such that a thorough consideration of this compound’s in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and health authorities’ approval, DCA has been introduced in off-label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are few thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA’s benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in it.

Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient’s characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier’s gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions.

N-methylbupropion was selected as a potential prodrug from our in vitro screening of analogues of bupropion described in the preceding paper. This study describes in vivo pharmacokinetics of N-methylbupropion in the guinea-pig animal model, which is reported to best predict human metabolism of bupropion. The suitability of the guinea pig was established by studying N-demethylation of N-methylbupropion using S9 liver fractions. An LC-MS method was developed and validated to measure N-methylbupropion, bupropion and their metabolites in plasma and brain tissue. In separate studies, the prodrug was delivered by intraperitoneal injection (IP) to assess hepatic metabolism and then by oral gavage (PO) to assess the contribution from intestinal enzymes. Bupropion was administered in parallel. The pharmacokinetic profile of bupropion and N-methylbupropion were not comparable when dosed by intraperitoneal injection but when dosed orally, N-methylbupropion showed a comparable bupropion and metabolite PK plasma profile to bupropion. Plasma and brain levels of N-methylbupropion show that it is extensively metabolized to bupropion and its metabolites, and N-methyl-threo-hydrobupropion. This data coupled to the reduced DAT and NET system in vitro activity described in paper 1 would suggest that the N-methyl derivative of bupropion may have potential as an oral prodrug of bupropion in humans.

Tuberculosis is still the leading cause of death by a single infectious agent. Effective chemotherapy has been used and improved since the 1950s, but strains resistant to this therapy and most antibacterial drugs on the market are emerging. Only 10 new drugs are in clinical trials, and two of them have already demonstrated resistance. This paper gives an overview of current treatment options against tuberculosis and points out a promising approach of discovering new effective drugs. The serine production pathway is composed of three enzymes (SerA1, SerC and SerB2), which are considered essential for bacterial growth, and all of them are considered as a therapeutic drug target. Their crystal structure are described and essential regulatory domains pointed out. Sequence alignment with similar enzymes in other host would help to identify key residues to target in order to achieve selective inhibition. Currently, only inhibitors of SerB2 are described in the literature. However, inhibitors of human enzymes are discussed, and could be used as a good starting point for a drug discovery program. The aim of this paper is to give some guidance for the design of new hits for every enzyme in this pathway.

Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions, highlighting their potential as therapeutic targets. This paper reviews the structure and function of the four classes of human HDACs. While four HDAC inhibitors are currently available for treating hematological malignancies, numerous others are undergoing clinical trials. However, their non-selective toxicity necessitates ongoing research into safer and more efficient class-selective or isoform-selective inhibitors. Computational methods have aided the discovery of HDAC inhibitors with the desired potency and/or selectivity. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, three-dimensional quantitative structure–activity relationships, and structure-based virtual screening (molecular docking). Moreover, recent developments in the field of molecular dynamics simulations, combined with Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques, have improved the prediction of ligand binding affinity. In this review, we delve into the ways in which these methods have contributed to designing and identifying HDAC inhibitors.

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

There are a wide variety of phytochemicals collectively known as polyphenols. Their structural diversity results in a broad range of characteristics and biological effects. Polyphenols can be found in a variety of foods and drinks, including fruits, cereals, tea, and coffee. Studies both in vitro and in vivo, as well as clinical trials, have shown that they possess potent antioxidant activities, numerous therapeutic effects, and health advantages. Dietary polyphenols have demonstrated the potential to prevent many health problems, including obesity, atherosclerosis, high blood sugar, diabetes, hypertension, cancer, and neurological diseases. In this paper, the protective effects of polyphenols and the mechanisms behind them are investigated in detail, citing the most recent available literature. This review aims to provide a comprehensive overview of the current knowledge on the role of polyphenols in preventing and managing chronic diseases. The cited publications are derived from in vitro, in vivo, and human-based studies and clinical trials. A more complete understanding of these naturally occurring metabolites will pave the way for the development of novel polyphenol-rich diet and drug development programs. This, in turn, provides further evidence of their health benefits.

Background: We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. Methods: The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. Results: For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. Conclusions: CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries’ scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.

Several biologically active compounds involved in the green synthesis of silver and gold nanoparticles have been isolated from snail mucus and characterized. This paper presents a successful method for the application of snail mucus from Cornu aspersum as a bioreducing agent of copper sulfate and as a biostabilizer of the copper oxide nanoparticles (CuONPs-Muc) obtained. The synthesis at room temperature and neutral pH yielded nanoparticles with a spherical shape and an average diameter of 150 nm. The structure and properties of CuONPs-Muc were characterized using various methods and techniques, such as ultraviolet–visible spectroscopy (UV–vis), high-performance liquid chromatography (HPLC), one-dimensional polyacrylamide gel electrophoresis (1D-PAGE), up-conversion infrared spectroscopy Fourier transform (FTIR), scanning electron microscopy combined with energy dispersive spectroscopy (SEM/EDS), Raman spectroscopy and imaging, thermogravimetric analysis (TG-DSC), etc. Mucus proteins with molecular weights of 30.691 kDa and 26.549 kDa were identified, which are involved in the biogenic production of CuONPs-Muc. The macromolecular shell of proteins formed around the copper ions contributes to a higher efficiency of the synthesized CuONPs-Muc in inhibiting the bacterial growth of several Gram-positive (Bacillus subtilis NBIMCC2353, Bacillus spizizenii ATCC 6633, Staphylococcus aureus ATCC 6538, Listeria innocua NBIMCC8755) and Gram-negative (Escherichia coli ATCC8739, Salmonella enteitidis NBIMCC8691, Salmonella typhimurium ATCC 14028, Stenotrophomonas maltophilia ATCC 17666) bacteria compared to baseline mucus. The bioorganic synthesis of snail mucus presented here provides CuONPs-Muc with a highly pronounced antimicrobial effect. These results will expand knowledge in the field of natural nanomaterials and their role in emerging dosage forms.

The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization.

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the environmental aspects of their use and subsequent emissions usually remain less explored. However, as with other human activities, drug production, trade, and consumption of drugs may leave their environmental mark. Therefore, this paper aims to review the occurrence of illicit drugs in surface waters and their bioaccumulation and toxicity in fish. Illicit drugs of different groups, i.e., psychostimulants (methamphetamines/amphetamines, cocaine, and its metabolite benzoylecgonine) and depressants (opioids: morphine, heroin, methadone, fentanyl), can reach the aquatic environment through wastewater discharge as they are often not entirely removed during wastewater treatment processes, resulting in their subsequent circulation in nanomolar concentrations, potentially affecting aquatic biota, including fish. Exposure to such xenobiotics can induce oxidative stress and dysfunction to mitochondrial and lysosomal function, distort locomotion activity by regulating the dopaminergic and glutamatergic systems, increase the predation risk, instigate neurological disorders, disbalance neurotransmission, and produce histopathological alterations in the brain and liver tissues, similar to those described in mammals. Hence, this drugs-related multidimensional harm to fish should be thoroughly investigated in line with environmental protection policies before it is too late. At the same time, selected fish species (e.g., Danio rerio, zebrafish) can be employed as models to study toxic and binge-like effects of psychoactive, illicit compounds.

This Special Issue, which focused on methyl-containing pharmaceuticals, collected different papers and reviews on this topic [...]

COVID-19, caused by SARS-CoV-2, has emerged as the most destructive emerging infectious disease of the 21st century. Vaccination is an effective method to combat viral diseases. However, due to the constant mutation of the virus, new variants may weaken the efficacy of vaccines. In the current field of new coronavirus research, viral protease inhibitors have emerged as a highly regarded therapeutic strategy. Nevertheless, existing viral protease inhibitors do not fully meet the therapeutic needs. Therefore, this paper turned to traditional Chinese medicine to explore new active compounds. This study focused on 24 isolated compounds from Acorus calamus L. and identified 8 active components that exhibited significant inhibitory effects on SARS-CoV-2 PLpro. Among these, the compound 1R,5R,7S-guaiane-4R,10R-diol-6-one demonstrated the best inhibitory activity with IC50 values of 0.386 ± 0.118 μM. Additionally, menecubebane B and neo-acorane A exhibited inhibitory activity against both Mpro and PLpro proteases, indicating their potential as dual-target inhibitors. The molecular docking results confirmed the stable conformations of these compounds with the key targets and their good activity. ADMET and Lipinski’s rule analyses revealed that all the small molecule ligands possessed excellent oral absorption properties. This study provides an experimental foundation for the discovery of promising antiviral lead compounds.

In this paper, we present the identification of polymorphisms at an early stage, identified by applying non-standard methods such as SAXS. We provide an analytical approach to polymorphism in the quality/purity of an active pharmaceutical ingredient (API), supplied to a generic company by two different suppliers (i.e., manufacturers). Changes in thermodynamic polymorphism firstly become visible in traces in the larger crystal lattices, which are visible on the SAXS spectrum only using the logarithmic scale, as shown in the result figures. Hence, we are here on the trail of the beginning of a new polymorph in nicomorphine, whose crystal waviness at the early stage is visible only in the additional symmetrical peaks identified and calculated using SAXS, while the chemical analyses excluded all kinds of chemical impurities. The chemical and structural properties were studied using the following techniques: SAXS, WAXS, DSC, dissolution, Raman spectroscopy, and FTIR. Only the SAXS technique could identify crucial differences and calculate the additional signals related to giant crystals, whilst a standard method such as WAXS showed none, and nor did the chemical analyses, such as Raman spectroscopy and FT-IR. This means that due to water in crystallization (known in nicomorphine) or thermodynamic waviness, the formation of the new polymorph starts first in traces, which become visible at larger distances from the crystal lattice, detectible only in the SAXS range. This is a very important premise and hypothesis for further research, and we believe that this work lays a new stone in understanding the origin of new unknown polymorphs and their mixtures. Therefore, the aim of this work is to show that the use of non-standard methods (i.e., SAXS) can be of great benefit to API analysis and the identification of polymorphic changes in the early phase, which can cause varied stability, solubility and bioavailability and thus different therapeutic effects or side effects.

Inappropriate expression of histone deacetylase (HDAC-6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signalling pathway are common aberrations observed in cancers. LASSBio-2208, has been previously described as a dual inhibitor in the nanomolar range of HDAC-6 and PI3Kα and is three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its drug metabolism and pharmacokinetics (DMPK) in vitro profile. Our studies have demonstrated that LASSBio-2208 has moderate cytotoxic potency on breast cancer cell line MCF-7 (IC50 = 23 µM), human leukaemia cell line CCRF-CEM (IC50 = 8.54 µM) and T lymphoblast cell line MOLT-4 (IC50 = 7.15 µM), with no cytotoxic effect on human peripheral blood mononuclear cells (hPBMC). In addition, it has a good antiproliferative effect on MCF-7 cells (IC50 = 5.44 µM), low absorption by parallel artificial membrane permeability—gastrointestinal tract (PAMPA—GIT) and low permeation by parallel artificial membrane permeability—blood–brain barrier (BBB) (PAMPA—BBB), exhibiting high metabolic stability in rat plasma. Moreover, LASSBio-2208 exhibited synergism when combined with getadolisib and tubastatin A, using the concentrations corresponding to their CC50 values on MOLT-4 and CCRF-CEM cells.

“Click reactions” are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation. Although the biological results were not adequate for a potential radiopharmaceutical, the outcome of this work is valuable since the use of automated platforms is required for the reliable and reproducible preparation of PET radiopharmaceuticals in GMP conditions while limiting the radiation dose rates to the personnel.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

The year 2024 marks the 125th anniversary of aspirin, still one of the most frequently used drugs worldwide. Despite its veritable age, it is still relevant in pharmacotherapy and its use has spread to new areas over time. Due to aspirin’s multiple pharmacological actions unified in one single molecule (i.e., analgesic, antipyretic, anti-inflammatory, antithrombotic, and antiviral effects), it continues to attract considerable attention in the scientific community and is subject to intense basic and clinical research. In fact, recent results confirmed aspirin’s potential role as an antiviral drug and as an agent that can block harmful platelet functions in inflammatory/immunological processes. These features may open up new horizons for this ancient drug. The future of aspirin looks, therefore, bright and promising. Aspirin is not yet ready for retirement; on the contrary, its success story continues. This 125th anniversary paper will concisely review the various therapeutic uses of aspirin with a particular emphasis on the latest research results and their implications (e.g., use as an antiviral agent). In addition, the reader is provided with future perspectives for this remarkable drug.

Physical interactions between proteins are often difficult to decipher. The aim of this paper is to present an algorithm that is designed to recognize binding patches and supporting structural scaffolds of interacting heterodimer proteins using the Gaussian Network Model (GNM). The recognition is based on the (self) adjustable identification of kinetically hot residues and their connection to possible binding scaffolds. The kinetically hot residues are residues with the lowest entropy, i.e., the highest contribution to the weighted sum of the fastest modes per chain extracted via GNM. The algorithm adjusts the number of fast modes in the GNM’s weighted sum calculation using the ratio of predicted and expected numbers of target residues (contact and the neighboring first-layer residues). This approach produces very good results when applied to dimers with high protein sequence length ratios. The protocol’s ability to recognize near native decoys was compared to the ability of the residue-level statistical potential of Lu and Skolnick using the Sternberg and Vakser decoy dimers sets. The statistical potential produced better overall results, but in a number of cases its predicting ability was comparable, or even inferior, to the prediction ability of the adjustable GNM approach. The results presented in this paper suggest that in heterodimers at least one protein has interacting scaffold determined by the immovable, kinetically hot residues. In many cases, interacting proteins (especially if being of noticeably different sizes) either behave as a rigid lock and key or, presumably, exhibit the opposite dynamic behavior. While the binding surface of one protein is rigid and stable, its partner’s interacting scaffold is more flexible and adaptable.

The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas.

Black Phosphorus (BP) is a new semiconductor material with excellent biocompatibility, degradability, and optical and electrophysical properties. A growing number of studies show that BP has high potential applications in the biomedical field. This article aims to systematically review the research progress of BP composite medical materials in the field of tissue engineering, mining BP in bone regeneration, skin repair, nerve repair, inflammation, treatment methods, and the application mechanism. Furthermore, the paper discusses the shortcomings and future recommendations related to the development of BP. These shortcomings include stability, photothermal conversion capacity, preparation process, and other related issues. However, despite these challenges, the utilization of BP-based medical materials holds immense promise in revolutionizing the field of tissue repair.

The essential role of nicotinamide adenine dinucleotide+ (NAD+) in redox reactions during oxidative respiration is well known, yet the coenzyme and regulator functions of NAD+ in diverse and important processes are still being discovered. Maintaining NAD+ levels through diet is essential for health. In fact, the United States requires supplementation of the NAD+ precursor niacin into the food chain for these reasons. A large body of research also indicates that elevating NAD+ levels is beneficial for numerous conditions, including cancer, cardiovascular health, inflammatory response, and longevity. Consequently, strategies have been created to elevate NAD+ levels through dietary supplementation with NAD+ precursor compounds. This paper explores current research regarding these therapeutic compounds. It then focuses on the NAD+ regulation of IL-13 signaling, which is a research area garnering little attention. IL-13 is a critical regulator of allergic response and is associated with Parkinson’s disease and cancer. Evidence supporting the notion that increasing NAD+ levels might reduce IL-13 signal-induced inflammatory response is presented. The assessment is concluded with an examination of reports involving popular precursor compounds that boost NAD+ and their associations with IL-13 signaling in the context of offering a means for safely and effectively reducing inflammatory response by IL-13.

High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients’ tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence.

Aromatase inhibitors (AIs) show promising features as drugs to treat estrogen-responsive breast cancer as they block aromatase activity, the key enzyme in estrogen synthesis. The current AIs approved by the Food and Drug Administration for breast cancer treatment present severe adverse effects. For these reasons, it is important to develop of new AIs that are more specific and sensitive. In this paper, we report the synthesis and the characterization of new nonsteroidal aromatase AIs containing triazoles moieties for the treatment of hormone-dependent breast cancer in post-menopausal women. A new series of 1,2,3-triazole based molecules were successfully synthetized and their chemical structures were determined from the spectral data (FT-IR, 13C NMR, 1H NMR, mass spectroscopy) and micro-analytical data. Additionally, the physical properties of the newly synthesized derivatives were reported. The novel compounds were also tested for their anticancer activity in both breast cancer (MCF7 and T-47D) and normal breast (MCF 10A) cell lines, evaluating their effect on cell proliferation, migration, and invasion. The results revealed that the compounds exhibited promising and specific anti-cancer action.

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation.

More than 30 years ago, in 1990, three independent research groups published several papers demonstrating that genetics could be performed in vitro in the absence of living organisms or cells [...]

The extraction of bioactive compounds of pharmaceutical interest from natural sources has been significantly explored in recent decades. However, the extraction techniques used were not very efficient in terms of time and energy consumption; additionally, the solvents used for the extraction were harmful for the environment. To improve the environmental impact of the extractions and at the same time increase the extraction yields, several new extraction techniques were developed. Among the most used ones are ultrasound-assisted extraction and microwave-assisted extraction. These extraction techniques increased the yield and selectivity of the extraction in a smaller amount of time with a decrease in energy consumption. Nevertheless, a high volume of organic solvents was still used for the extraction, causing a subsequent environmental problem. Neoteric solvents appeared as green alternatives to organic solvents. Among the neoteric solvents, deep eutectic solvents were evidenced to be one of the best alternatives to organic solvents due to their intrinsic characteristics. These solvents are considered green solvents because they are made up of natural compounds such as sugars, amino acids, and carboxylic acids having low toxicity and high degradability. In addition, they are simple to prepare, with an atomic economy of 100%, with attractive physicochemical properties. Furthermore, the huge number of compounds that can be used to synthesize these solvents make them very useful in the extraction of bioactive compounds since they can be tailored to be selective towards a specific component or class of components. The main aim of this paper is to give a comprehensive review which describes the main properties, characteristics, and production methods of deep eutectic solvents as well as its application to extract from natural sources bioactive compounds with pharmaceutical interest. Additionally, an overview of the more recent and sustainable extraction techniques is also given.

The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-β-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.

The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research.

The aim of the study was to achieve effective colon anticancer immunotherapy using the alkaloid berberine. In the presented paper we attempt to develop a formulation of berberine loaded into liposomal carriers using the vitamin C gradient method, characterized by efficient drug encapsulation, high stability during long-term storage, low drug release in human plasma with specific cytotoxicity towards colon cancer cells. Liposomal berberine was responsible for the induction of oxidative stress, the presence of Ca2+ ions in the cytosol, the reduction of Δψm, and ATP depletion with a simultaneous lack of caspase activity. Moreover, treatment with liposomal berberine led to CRT exposure on the surface of cancer cells, extracellular ATP, and HMGB1 release. The above-described mechanism of action was most likely associated with ICD induction, contributing to the increased number of phagocytic cancer cells. We have shown that cancer cells treated with liposomal berberine were phagocytosed more frequently by macrophages compared to the untreated cancer cells. What is more, we have shown that macrophage pre-treatment with liposomal berberine led to a 3-fold change in the number of phagocytosed SW620 cancer cells. The obtained results provide new insights into the role of berberine in maintaining the immune response against colorectal cancer.

Among the human T-lymphotropic virus (HTLV) types, HTLV-1 is the most prevalent, and it has been linked to a spectrum of diseases, including HAM/TSP, ATLL, and hyperinfection syndrome or disseminated strongyloidiasis. There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. To address this, a comprehensive review was conducted, analyzing 30 recent papers from databases PubMed, CAPES journals, and the Virtual Health Library (VHL). The studies encompassed a wide range of therapeutic approaches, including antiretrovirals, immunomodulators, antineoplastics, amino acids, antiparasitics, and even natural products and plant extracts. Notably, the category with the highest number of articles was related to drugs for the treatment of ATLL. Studies employing mogamulizumab as a new perspective for ATLL received greater attention in the last 5 years, demonstrating efficacy, safe use in the elderly, significant antitumor activity, and increased survival time for refractory patients. Concerning HAM/TSP, despite corticosteroid being recommended, a more randomized clinical trial is needed to support treatment other than corticoids. The study also included a comprehensive review of the drugs used to treat disseminated strongyloidiasis in co-infection with HTLV-1, including their administration form, in order to emphasize gaps and facilitate the development of other studies aiming at better-directed methodologies. Additionally, docking molecules and computer simulations show promise in identifying novel therapeutic targets and repurposing existing drugs. These advances are crucial in developing more effective and targeted treatments against HTLV-1 and its related diseases.

Demonstrating biosimilarity entails comprehensive analytical assessment, clinical pharmacology profiling, and efficacy testing in patients for at least one medical indication, as required by the U.S. Biologics Price Competition and Innovation Act (BPCIA). The efficacy testing can be waived if the drug has known pharmacodynamic (PD) markers, leaving most therapeutic proteins out of this concession. To overcome this, the FDA suggests that biosimilar developers discover PD biomarkers using omics technologies such as proteomics, glycomics, transcriptomics, genomics, epigenomics, and metabolomics. This approach is redundant since the mode-action-action biomarkers of approved therapeutic proteins are already available, as compiled in this paper for the first time. Other potential biomarkers are receptor binding and pharmacokinetic profiling, which can be made more relevant to ensure biosimilarity without requiring biosimilar developers to conduct extensive research, for which they are rarely qualified.

Organoselenium compounds are well-known for their numerous biocapacities, which result from the uniqueness of the selenium atom and the possibility of constructing heterorganic molecules that can mimic the activity of selenoenzymes, crucial for a multitude of important physiological processes. In this paper, we have synthesized a series of N-substituted benzisoselenazolones and corresponding diphenyl diselenides possessing lipophilic long carbon chains, solely or with additional polar insets: phenyl linkers and ester groups. Evaluation of their antioxidant and cytotoxic activity revealed an increased H2O2-reduction potential of diphenyl diselenides bearing N-octyl, ethyl N-(12-dodecanoate)- and N-(8-octanoate) groups, elevated radical scavenging activity of 2,2′-diselenobis(N-dodecylbenzamide) and a promising cytotoxic potential of N-(4-dodecyl)phenylbenzisoselenazol-3(2H)-one.

Molecular hydrogen (H2) is a colorless, odorless, and tasteless gas which displays non-toxic features at high concentrations. H2 can alleviate oxidative damage, reduce inflammatory reactions and inhibit apoptosis cascades, thereby inducing protective and repairing effects on cells. H2 can be transported into the body in the form of H2 gas, hydrogen-rich water (HRW), hydrogen-rich saline (HRS) or H2 produced by intestinal bacteria. Accumulating evidence suggest that H2 is protective against multiple ophthalmic diseases, including cataracts, dry eye disease, diabetic retinopathy (DR) and other fields. In particular, H2 has been tested in the treatment of dry eye disease and corneal endothelial injury in clinical practice. This medical gas has brought hope to patients suffering from blindness. Although H2 has demonstrated promising therapeutic potentials and broad application prospects, further large-scale studies involving more patients are still needed to determine its optimal application mode and dosage. In this paper, we have reviewed the basic characteristics of H2, and its therapeutic effects in ophthalmic diseases. We also focus on the latest progress in the administration approaches and mechanisms underlying these benefits.

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for αvβ3 integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation. Furthermore, the therapeutic properties of the [198Au]AuNPs were evaluated in vitro on U87MG cells in terms of cell survival, suggesting that these [198Au]AuNPs are a useful basis for future therapeutic concepts.

Cancer is still one of the major factors threatening public health, with morbidity and mortality rates at the forefront of the world. Clinical drawbacks, such as high toxicity and side effects of drug therapy, and easy recurrence after surgery affect its therapeutic effect. Gas signaling molecules are essential in maintaining biological homeostasis and physiological functions as specific chemical substances for biological information transfer. In recent years, the physiological regulatory functions of gas molecules in the cancer process have been gradually revealed and have shown broad application prospects in tumor therapy. In this paper, standard gas therapies are classified and introduced. Taking H2, CO2, NO, CO, H2S, and SO2 gases as examples, the research progress and application of gas therapies in malignant tumors are mainly introduced in terms of biological characteristics, anticancer mechanisms, and treatment strategies. Finally, the problems and prospects for developing gases as anticancer drugs are outlined.

Metal nanoparticles (NPs) have garnered considerable attention, due to their unique physicochemical properties, that render them promising candidates for various applications in medicine and industry. This article offers a comprehensive overview of the most recent advancements in the manufacturing, characterization, and biomedical utilization of metal NPs, with a primary focus on silver and gold NPs. Their potential as effective anticancer, anti-inflammatory, and antimicrobial agents, drug delivery systems, and imaging agents in the diagnosis and treatment of a variety of disorders is reviewed. Moreover, their translation to therapeutic settings, and the issue of their inclusion in clinical trials, are assessed in light of over 30 clinical investigations that concentrate on administering either silver or gold NPs in conditions ranging from nosocomial infections to different types of cancers. This paper aims not only to examine the biocompatibility of nanomaterials but also to emphasize potential challenges that may limit their safe integration into healthcare practices. More than 100 nanomedicines are currently on the market, which justifies ongoing study into the use of nanomaterials in medicine. Overall, the present review aims to highlight the potential of silver and gold NPs as innovative and effective therapeutics in the field of biomedicine, citing some of their most relevant current applications.

Background: Several solutions are now proposed to provide indoor illumination with so-called artificial white light or simulated daylight (SDL-PDT), resulting in an effective treatment for actinic keratosis (AK). However, the optimal PpIX-weighted light dose is still debated. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose and is a key parameter for the efficacy of the treatment. Objectives: The paper aims to report the clinical outcomes of SDL-PDT when using the PpIX-weighted light dose of 4 J/cm2, in patients treated for AK lesions of the scalp or the face at our medical dermatology center (ClinicalTrials.gov NCT052036). Methods: A total of 30 patients (16 males, 14 females), with a mean age of 71.0 ± 10.2, with phototype 1 (16 patients) and phototype 2 (14 patients) with grade I–II AK were treated with a drug light interval (DLI) of 10 min and a light exposure of 35 min (Dermaris, Surgiris, Croix, France), corresponding to a PpIX-weighted light dose of 4 J/cm2. The primary endpoint was the cure rate of patients at six months post-treatment. Secondary endpoints included scores of pain, erythema, crusts, and discomfort during or/and post the treatment. Results: In total, 762 AK were treated. Six months following treatment, the cure rate of the patients was 77%. The median pain score was less than 1 out of 10 for most of the patients. Erythema was observed in all patients and lasted 3 days (±1.5 day). Crusts were seen in 28 patients. Discomfort was reported as mild or less in more than 97% of patients. Conclusions: The shortening of the PpIX-weighted light dose to 4 J/cm2, corresponding to an illumination duration of 35 min with the Dermaris, does not modify the efficacy of the SDL-PDT. This observation is in agreement with recent published data demonstrating that the light dose can be reduced. Furthermore, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.

Transdermal administration of chemo therapeutics into burn healing may be an effective treatment to reduce toxic side effects and improve patient compliance for burns. As a transdermal delivery system, Camelina lipid droplets (CLDs) have received great attention due to their biocompatibility, high drug payload, and rapid absorption. However, the absorbed-related mechanisms of Camelina lipid droplets have not yet been reported. Thus, this paper not only demonstrated that CLD can accelerate skin burn healing through promoting hFGF2 absorption, but also elucidated the mechanism between the skin tissue and keratinocytes using Franz, HE staining, DSC, FTIR spectroscopy, and atomic force microscopy with the presence of CLD-hFGF2 freeze-dried powder. We found that the cumulative release rate of CLD-hFGF2 freeze-dried powder was significantly higher than that of free hFGF2 freeze-dried powder into the skin. At the same time, CLD can change the structure and content of lipids and keratin to increase the permeability of hFGF2 freeze-dried powder in skin tissue. Unlike the free state of hFGF2, the biophysical properties of single cells, including height and adhesion force, were changed under CLD-hFGF2 freeze-dried powder treatment. Meanwhile, CLD-hFGF2 freeze-dried powder was more easily taken up through keratinocytes without damaging cell integrity, which provided a new viewpoint for understanding the absorption mechanism with the CLD system for cellular physiology characteristics. Overall, our findings demonstrated that CLD could break through the stratum corneum (SC) barrier and elucidated the transport mechanism of lipid droplets in skin tissue, which provides a crucial guideline in drug delivery applications for future engineering.

The US FDA’s new guideline suggests using “Generally Accepted Science Knowledge” (GASK) to develop nonclinical testing protocols for developing drugs and biologicals to remove unnecessary testing. Interpreting acceptable scientific knowledge as a rational approach has motivated the author to suggest substantial changes to the development of biosimilars, as demonstrated in this paper. The FDA can accept these suggestions without requiring any legislative change to the Act that defines such requirements. Suggested here is the waiving of clinical efficacy testing due to its lower sensitivity compared to analytical and functional testing and pharmacokinetic profiling. Also questioned is the need to test pharmacodynamic markers that do not correlate with clinical response and find new biomarkers requiring extensive testing to validate their use. Should the FDA accept these scientifically rational suggestions, it will significantly reduce the time and cost of approving biosimilars without safety or efficacy risk, as justified based on acceptable scientific knowledge and rationality.

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla. No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla. In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds (DL1–DL13 and PA1–PA7) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

Sulfated polysaccharides from seaweed are highly active natural substances with valuable applications. In the present paper, attempts have been made to discuss the physicochemical and structural features of polysaccharides isolated from red marine alga Alsidium corallinum (ACPs) and their protective effect in hepatic impairments induced by tebuconazole (TEB) in male adult rats. Structural features were determined using high-performance liquid chromatography, Fourier-transformed infrared, and solid-state 1H and 13C-Nuclear magnetic resonance analysis. ACPs are found to be hetero-sulfated-anionic polysaccharides that contain carbohydrates, sulfate groups, and uronic acids. In vitro biological activities suggested the effective antioxidant and antimicrobial capacities of ACPs. For antioxidant testing in vivo, the biochemical analysis and plasma profiles displayed that oral administration of ACPs could mitigate blood lipid indicators, including total cholesterol, triglyceride, low and high-density lipoprotein cholesterol, and bilirubin. Liver function indexes involving alanine aminotransferase and aspartate aminotransferase showed that ACPs possessed prominent antioxidant activities. Additionally, the intervention of ACPs potentially inhibited lipid peroxidation, protein oxidation, key enzymes of lipid metabolism (A. corallinum monosaccharides bound 1JIJ, 1HD2, and 1WL4 receptors with acceptable affinities, which, together with deep embedding and molecular interactions, support the antioxidant, antimicrobial, and hypolipidemic outlined effects in the in vitro and in vivo findings. Given their prominent antioxidant effects, ACPs are promising candidates for liver diseases and must be considered in pharmaceutical applications.

Fluoroquinolones (FQs) are widely used drugs around the world. This is a result of their broad spectrum of antibacterial activity, high bioavailability, and known efficacy. Since they appeared on the market, their prescribing frequency has gradually increased. In 2011, FQs became the third most prescribed class of antibiotics in the US. Widespread use of these drugs resulted in an increasing number of reported side effects. In 2016, the FDA warned about significant side effects, including mental disorders in the form of anxiety, psychotic symptoms, insomnia, and depression. Psychiatric adverse reactions to FQs occur with a frequency of 1 to 4.4% and the mechanism of their formation is not entirely clear. It is believed that the antagonistic effect of FQs on the GABA receptor or interaction with the main receptor for the glutamatergic system—NMDA—is responsible for this. The paper is a structured review of 68 selected publications and the latest summary of CNS adverse effects that occur during FQ use. Prescribers should be aware of the risk factors for FQ toxicity, including elderly patients with underlying medical conditions or receiving concomitant medication; however, these adverse events may also occur in other groups of patients.