Pharmacological Trials Research Articles

Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review.

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.

Abstract 14710: The Landscape of Pharmacological Interventional Trials for the Treatment or Prevention of Coronary Artery Disease: Analysis of clinicaltrials.gov Listings From 2008 to 2022

Background: Coronary artery disease (CAD) has been the leading cause of death and disability over the past two decades. Aims: To systematically assess the characteristics and trends of clinical trials pertaining to the treatment or prevention of CAD. Methods: The analysis included studies that (1) were registered in the ClinicalTrials.gov database from 2008 to 2022; (2) involved ≥1 pharmacological intervention; and (3) were designed to treat or prevent CAD or its complications. Study records were downloaded on December 27, 2022 for screening and analysis. Pharmacological interventions were classified according to the World Health Organization Anatomical Therapeutic Chemical Classification System. Annual trends by the year of study registration were assessed with a two-sided Cochran-Armitage test. Results: A total of 1,619 trials were identified from a pool of 437,319 studies. There was a declining trend in the number of CAD trials (Figure A). The majority of trials (47.5%) were targeted to enroll ≤100 participants, while 39.4% targeted 101-1000 participants, 10.5% targeted 1001-5000 participants, and 2.6% were mega-trials (>5000 participants). The distribution of study duration was as follows: ≤12 months (25.3%), 13-60 months (67.3%), and >60 months (7.5%). Of note, the open-label design was more commonly employed in treatment trials (41.8% vs. 31.6%; p=0.02), while the parallel assignment was more frequently utilized in prevention trials (88.8% vs. 82.0%; p=0.03). In addition, declining trends in the proportions of phase 3 trials (p=0.0008; Figure B) and trials of lipid-modifying (p=0.0043) or anti-thrombotic agents (p=0.03; Figure C) were observed. Conclusion: Between 2008 and 2022, the clinical trial landscape of CAD diminished and was mainly shaped by studies with small to moderate sample sizes and short to intermediate follow-up duration. Research focus trended toward study interventions other than anti-thrombotic or lipid-modifying agents.

Treatment of schizotypal disorder: a protocol for a systematic review of the evidence and recommendations for clinical practice

IntroductionSchizotypal disorder is associated with a high level of disability at an individual level and high societal costs. However, clinical recommendations for the treatment of schizotypal disorder are scarce and...

Zavegepant Intranasal Spray for Migraines.

The objective is to review the pharmacology, efficacy, and safety of intranasal zavegepant in the acute treatment of migraine with or without aura. PubMed, Embase database, and ClinicalTrials.gov were searched using the following terms: Zavzpret, Zavegepant, BHV-3500, and migraine. Articles published in English from January 2013 to September 2023 related to pharmacology, safety, efficacy, and clinical trials were assessed. In a phase 2/3 trial, zavegepant 10 and 20 mg were more effective than placebo on primary endpoints of freedom of pain (22.5%, 23.1%, and 15.5%, respectively), and freedom from most bothersome symptoms (MBSs) (41.9%, 47.9%, and 33.7%, respectively) 2 hours after treatment. The incidence of adverse effects for both doses was similar to placebo. In a phase 3 trial, zavegepant 10 mg was compared with placebo. Two hours after treatment, more patients in the zavegepant group achieved pain freedom (24% vs 15%) and relief from MBSs (40% vs 31%) compared with placebo. Common adverse events included dysgeusia (21% zavegepant vs 5% placebo) and nasal discomfort (5% zavegepant vs 1% placebo). Zavegepant is indicated for acute treatment of migraine with or without aura in adults. Zavegepant method of administration and prompt relief of migraine symptoms may be an attractive alternative to triptans for those in need of relief. Zavegepant may be a convenient and useful acute treatment option for migraines with and without aura.

Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections.

To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL. Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed. A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference -13.2%; 95% CI [-30.0 to 3.5]). Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections. SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.

The role of epigenetics in anxiety disorders.

Anxiety disorders (ADs) are extremely common psychiatric conditions that frequently co-occur with other physical and mental disorders. The pathophysiology of ADs is multifaceted and involves intricate connections among biological elements, environmental stimuli, and psychological mechanisms. Recent discoveries have highlighted the significance of epigenetics in bridging the gap between multiple risk factors that contribute to ADs and expanding our understanding of the pathomechanisms underlying ADs. Epigenetics is the study of how changes in the environment and behavior can have an impact on gene function. Indeed, researchers have found that epigenetic mechanisms can affect how genes are activated or inactivated, as well as whether they are expressed. Such mechanisms may also affect how ADs form and are protected. That is, the bulk of pharmacological trials evaluating epigenetic treatments for the treatment of ADs have used histone deacetylase inhibitors (HDACi), yielding promising outcomes in both preclinical and clinical studies. This review will provide an outline of how epigenetic pathways can be used to treat ADs or lessen their risk. It will also present the findings from preclinical and clinical trials that are currently available on the use of epigenetic drugs to treat ADs.

Protective effects of curcumin against osteoporosis and its molecular mechanisms: a recent review in preclinical trials.

Osteoporosis (OP) is one of the most common metabolic skeletal disorders and is commonly seen in the elderly population and postmenopausal women. It is mainly associated with progressive loss of bone mineral density, persistent deterioration of bone microarchitecture, and increased fracture risk. To date, drug therapy is the primary method used to prevent and treat osteoporosis. However, long-term drug therapy inevitably leads to drug resistance and specific side effects. Therefore, researchers are constantly searching for new monomer compounds from natural plants. As a candidate for the treatment of osteoporosis, curcumin (CUR) is a natural phenolic compound with various pharmacological and biological activities, including antioxidant, anti-apoptotic, and anti-inflammatory. This compound has gained research attention for maintaining bone health in various osteoporosis models. We reviewed preclinical and clinical studies of curcumin in preventing and alleviating osteoporosis. These results suggest that if subjected to rigorous pharmacological and clinical trials, naturally-derived curcumin could be used as a complementary and alternative medicine for the treatment of osteoporosis by targeting osteoporosis-related mechanistic pathways. This review summarizes the mechanisms of action and potential therapeutic applications of curcumin in the prevention and mitigation of osteoporosis and provides reference for further research and development of curcumin.

Effects of pharmacological and non-pharmacological interventions on physical activity outcomes in COPD: a systematic review and meta-analysis.

The effect of pharmacological and non-pharmacological interventions on physical activity (PA) outcomes is not fully elucidated in patients with COPD. The objectives of the present study were to provide estimation of treatment effects of all available interventions on PA outcomes in patients with COPD and to provide recommendations regarding the future role of PA outcomes in pharmacological trials. This review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported in line with PRISMA. Records were identified through searches of 12 scientific databases; the most updated search was performed in January 2023. 74 studies published from 2000 to 2021 were included, with a total of 8140 COPD patients. Forced expiratory volume in 1 s % predicted ranged between 31% and 74%, with a mean of 55%. Steps/day constituted the most frequently assessed PA outcome in interventional studies. Compared to usual care, PA behavioural modification interventions resulted in improvements in the mean (95% CI) steps/day when implemented alone (by 1035 (576-1493); p<0.00001) or alongside exercise training (by 679 (93-1266); p=0.02). Moreover, bronchodilator therapy yielded a favourable difference of 396 (125-668; p=0.004) steps/day, compared to placebo. PA behavioural modification and pharmacological interventions lead to significant improvements in steps/day, compared to control and placebo groups, respectively. Compared to bronchodilator therapy, PA behavioural modification interventions were associated with a 2-fold greater improvement in steps/day. Large-scale pharmacological studies are needed to establish an intervention-specific minimal clinically important difference for PA outcomes as well as their convergent validity to accelerate qualification as potential biomarkers and efficacy end-points for regulatory approval.

Abstract 112: Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypertension: An Individual-level Meta-analysis

Background: Orthostatic hypertension (OHTN) is associated with cardiovascular disease (CVD). We previously demonstrated how more intensive blood pressure (BP) treatment reduced orthostatic hypotension (OH) via a net increase in BP upon standing. Whether this effect also increased OHTN was not examined. Methods: We used pooled data from an individual participant data meta-analysis of 9 randomized BP pharmacologic treatment trials with seated and standing BP (search conducted through May 13, 2022). OHTN was defined as an increase in SBP ≥20 or DBP ≥10 mm Hg after changing from sitting to standing. Effects were examined overall and by baseline characteristics. Results: Of 31,124 participants with 315,497 standing BP assessments, 9% had OH, and 20% had OHTN at baseline. Trial effects were similar ( I 2 = 38.0%). During follow-up, 17% of those assigned more intensive treatment had OHTN, while 19% of those assigned less intensive treatment had OHTN. Intensive BP treatment significantly lowered OHTN risk (OR 0.93; 95% CI: 0.90, 0.96) ( Figure ). Effects were significantly greater among non-Black adults (OR 0.86 vs 0.97, P -interaction =0.003) and adults without diabetes (OR 0.88 vs 0.96; P -interaction =0.047). Effects did not differ by age≥75 years, sex, baseline seated BP≥130/≥80 mm Hg, obesity, stage 3 kidney disease, stroke, cardiovascular disease, standing SBP ≥140 mm Hg, or pre-randomization OHTN ( P -interactions ≥0.05). Conclusion: In this pooled cohort of adults with hypertension or higher CVD risk, OHTN was more common than OH and more intensive BP treatment reduced OHTN risk. The relationship between this effect with respect to CVD should be a focus of subsequent research.

Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Benzothiazole Derivatives of Chitosan and Their Derived Nanoparticles: Synthesis and In Vitro and In Vivo Antibacterial Effects.

In this work, we focused on synthesizing and assessing novel chitosan-based antibacterial polymers and their nanoparticles by incorporating benzothiazole substituents. The growing resistance to antibiotics has necessitated the search for alternative antimicrobial compounds. This study aimed to synthesize and evaluate chitosan-based polymers and nanoparticles with benzothiazole substituents for their antibacterial properties and toxicity. The benzothiazole derivatives of chitosan and their nanoparticles were synthesized through electrochemical coupling. The in vivo antibacterial efficacy was tested on white rats with induced peritonitis using a microbial suspension containing S. aureus and E. coli. Additionally, in vitro and in vivo toxicity assessments were conducted. The chitosan-based antibacterial systems showed significant in vivo antibacterial activity, surpassing that of unmodified chitosan and commercial antibiotics. Moreover, the toxicity studies revealed low toxicity levels of the synthesized derivatives, which did not differ significantly from native chitosan. The synthesized chitosan-based polymers and nanoparticles demonstrated potent antibacterial activity and low toxicity, highlighting their potential as effective alternatives to traditional antibiotics. Further investigations in pharmacology and preclinical trials are recommended to explore their application in clinical settings.

An Integrative Study on the Inhibition of Bone Loss via Osteo-F Based on Network Pharmacology, Experimental Verification, and Clinical Trials in Postmenopausal Women.

The inhibition of bone loss remains a challenge for postmenopausal women, considering the fact that only three anabolic treatments for osteoporosis have been approved by the FDA. This study aimed to investigate the osteogenic capacities of Osteo-F, a newly developed herbal formula, upon integrating network analysis and pre-clinical studies into clinical trials. The network pharmacology analysis showed that a potential mechanism of Osteo-F is closely related to osteoblast differentiation. Consistent with the predicted mechanism, Osteo-F treatment significantly enhanced bone matrix formation and mineralization with collagen expression in osteoblasts. Simultaneously, secreted bone-forming molecules were upregulated by Osteo-F. After the administration of Osteo-F to osteoporotic mice, the femoral BMD and osteocalcin in the serum and bone tissues were significantly improved. Subsequently, a randomized, double-blinded, placebo-controlled clinical trial showed that 253 mg of Osteo-F supplementation for 24 weeks resulted in significant improvements in the Z-score and serum osteocalcin levels of postmenopausal women compared to the placebo, thus indicating bone anabolic efficacy. In the current study, the bone anabolic effect of Osteo-F was determined by activating the differentiation and mineralization of osteoblasts through integrating experiments based on network analysis into clinical trials, with synchronized, reliable evidence, demonstrating that Osteo-F is a novel bone anabolic treatment in postmenopausal women.

FDG-PET markers of heterogeneity and different risk of progression in amnestic MCI.

Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. We looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG-PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An algorithm based on FDG-PET hypometabolism classified each subject into subtypes, then compared biomarker measures and clinical progression. Three subtypes emerged:hippocampal sparing-cortical hypometabolism, associated with younger age and the highest level of Alzheimer's disease (AD)-CSF pathology;hippocampal/cortical hypometabolism, associated with a high percentage of APOE ε3/ε4 or ε4/ε4carriers;medial-temporal hypometabolism, characterized by older age, the lowest AD-CSF pathology, the most severe hippocampal atrophy, and a benign course. Within the whole cohort, the severity of temporo-parietal hypometabolism, correlated with AD-CSF pathology and marked the rate of progression of cognitive decline. FDG-PET can distinguish clinically comparable aMCI at single-subject level with different risk of progression to AD dementia or stability. The obtained results can be useful for the optimization of pharmacological trials and automated-classification models. Algorithm based on FDG-PET hypometabolism demonstrates distinct subtypes across aMCI; Three different subtypes show heterogeneous biological profiles and risk of progression; The cortical hypometabolism is associated with AD pathology and cognitive decline; MTL hypometabolism is associated with the lowest conversion rate and CSF-AD pathology.

Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer’s disease

BackgroundThe current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis.MethodsHere we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS).ResultsThe SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD.ConclusionsSuch analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.

Potential biomarker of brain response to opioid antagonism in adolescents with eating disorders: a pilot study.

Eating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Youth aged 13-21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling. In 12 youth (16-21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD -0.08 ± 0.03; Cohen's d -1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen's d 1.25, p = 0.086). fMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing. https://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Turning the Spotlight to Cholinergic Pharmacotherapy of the Human Language System.

Even though language is essential in human communication, research on pharmacological therapies for language deficits in highly prevalent neurodegenerative and vascular brain diseases has received little attention. Emerging scientific evidence suggests that disruption of the cholinergic system may play an essential role in language deficits associated with Alzheimer's disease and vascular cognitive impairment, including post-stroke aphasia. Therefore, current models of cognitive processing are beginning to appraise the implications of the brain modulator acetylcholine in human language functions. Future work should be directed further to analyze the interplay between the cholinergic system and language, focusing on identifying brain regions receiving cholinergic innervation susceptible to modulation with pharmacotherapy to improve affected language domains. The evaluation of language deficits in pharmacological cholinergic trials for Alzheimer's disease and vascular cognitive impairment has thus far been limited to coarse-grained methods. More precise, fine-grained language testing is needed to refine patient selection for pharmacotherapy to detect subtle deficits in the initial phases of cognitive decline. Additionally, noninvasive biomarkers can help identify cholinergic depletion. However, despite the investigation of cholinergic treatment for language deficits in Alzheimer's disease and vascular cognitive impairment, data on its effectiveness are insufficient and controversial. In the case of post-stroke aphasia, cholinergic agents are showing promise, particularly when combined with speech-language therapy to promote trained-dependent neural plasticity. Future research should explore the potential benefits of cholinergic pharmacotherapy in language deficits and investigate optimal strategies for combining these agents with other therapeutic approaches.

An Update on Outcomes for COPD Pharmacological Trials: A COPD Investigators Report - Reassessment of the 2008 American Thoracic Society/European Respiratory Society Statement on Outcomes for COPD Pharmacological Trials.

Background: In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Measurements and Main Results: Endpoints, outcomes, and biomarkers have been revisited. The limitations of some of those reported in the American Thoracic Society/European Respiratory Society task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Because the "label-free" treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, and this will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help better identify the right patients to be treated with the new drugs.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

Dynorphin 1-17 biotransformation peptides: properties, challenges and solutions for future therapeutics development.

It is well established that endogenously produced dynorphin 1-17 (DYN 1-17) is susceptible to enzymatic degradation, producing a variety of unique fragments in different tissue matrices and disease pathologies. DYN 1-17 and its major biotransformation fragments have significant roles in neurological and inflammatory disorders upon interacting with opioid and non-opioid receptors at both central and peripheral levels, thus highlighting their potential as drug candidates. Nevertheless, their development as promising therapeutics is challenged by several issues. This review aims to provide the latest and comprehensive updates on DYN 1-17 biotransformed peptides, including their pharmacological roles, pharmacokinetic studies and relevant clinical trials. Challenges in their development as potential therapeutics and proposed solutions to overcome these limitations are also discussed.

Recent progression on phytochemicals and pharmacological properties of the filamentous cyanobacterium Lyngbya sp.

The distribution and phytochemistry of the non-nitrogen fixing, filamentous cyanobacterium (blue-green alga) Lyngbya sp., and the inherent antimicrobial and anticancer activities of its phycochemicals as well as of the biosynthesized nanoparticles as their pharmaceutical potencies are considered. Several phycocompounds of curio, apramide, apratoxin, benderamide, cocosamides, deoxymajusculamide, flavonoids, lagunamides, lipids, proteins, amino acids, lyngbyabellin, lyngbyastatin, majusculamide, peptides, etc. were isolated from Lyngbya sp., which had a lot of potential pharmaceutical activities; those compounds had antibacterial, antiviral, antifungal, anticancer, antioxidant, anti-inflammatory, ultraviolet protectant, and other activities. Particularly, several Lyngbya phycocompounds had potent antimicrobial potencies, seen through in vitro controlling of several frequently encountered multidrug-resistant (MDR) clinically belligerent strains of pathogenic bacteria isolated from clinical samples. The aqueous extracts of Lyngbya sp. were used for the synthesis of silver and copper oxide nanoparticles, which were used in pharmacological trials too. The nanoparticles biosynthesized with Lyngbya sp. had several uses such as biofuel, agro-based applications, in cosmetics, and industrial uses as biopolymers, and being potent antimicrobial and anticancer agents and in drug-delivery too, as medical applications. It could be concluded that the Lyngbya phycochemicals and the biosynthesized nanoparticles have future uses as antimicrobial namely as bacterial and fungal and anti-cancer agents, with promising medical and industrial uses.