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The American Journal of Pathology Nov 2023Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have... (Review)
Review
Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.
PubMed: 37156326
DOI: 10.1016/j.ajpath.2023.04.006 -
MedComm Oct 2023Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high-risk HPV infection can result in cervical precancerous lesions and... (Review)
Review
Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high-risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high-risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV-related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV-related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV-related cervical lesions.
PubMed: 37719443
DOI: 10.1002/mco2.368 -
Kidney360 Oct 2023Kidney disease is highly prevalent and affects approximately 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies... (Review)
Review
Kidney disease is highly prevalent and affects approximately 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies are incurable and often ineffective. Animal models are indispensable for understanding the pathophysiology of various kidney diseases and for preclinically testing novel remedies. In the last two decades, rodents continue to be the most used models for imitating human kidney diseases, largely because of the increasing availability of many unique genetically modified mice. Despite many limitations and pitfalls, animal models play an essential and irreplaceable role in gaining novel insights into the mechanisms, pathologies, and therapeutic targets of kidney disease. In this review, we highlight commonly used animal models of kidney diseases by focusing on experimental AKI, CKD, and diabetic kidney disease. We briefly summarize the pathological characteristics, advantages, and drawbacks of some widely used models. Emerging animal models such as mini pig, salamander, zebrafish, and drosophila, as well as human-derived kidney organoids and kidney-on-a-chip are also discussed. Undoubtedly, careful selection and utilization of appropriate animal models is of vital importance in deciphering the mechanisms underlying nephropathies and evaluating the efficacy of new treatment options. Such studies will provide a solid foundation for future diagnosis, prevention, and treatment of human kidney diseases.
Topics: Swine; Animals; Mice; Humans; Zebrafish; Swine, Miniature; Kidney; Models, Animal; Diabetic Nephropathies; Rodentia; Drosophila
PubMed: 37526653
DOI: 10.34067/KID.0000000000000227 -
Current Opinion in Nephrology and... Sep 2023Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the... (Review)
Review
PURPOSE OF REVIEW
Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the efficacy and safety of the treatment has spurred compelling mechanistic studies into the function of renal nerves and downstream impacts of denervation.
RECENT FINDINGS
A trial of the ultrasound Paradise Catheter system (RADIANCE II) found a 6.3 mmHg reduction in SBP relative to sham controls. A trial of the Symplicity Spyral system (SPYRAL HTN-ON MED) found an insignificant reduction in SBP relative to sham controls. Individuals were taking antihypertensive medications during the study, and investigators note the sham group experienced a larger medication burden than the denervated group. Recent preclinical studies have evaluated potential risks of renal denervation, how sympathetic activity broadly is affected, as well as identifying possible biomarkers to identify individuals where denervation would be more successful.
SUMMARY
Studies of renal denervation continue to find a robust antihypertensive effect, especially in studies wherein medications are withdrawn. Further investigation into mechanisms and indicators for usage of the technique will be important in identifying the patient population most likely to benefit from usage of renal denervation.
Topics: Humans; Hypertension; Antihypertensive Agents; Sympathectomy; Kidney; Denervation; Blood Pressure; Treatment Outcome
PubMed: 37530084
DOI: 10.1097/MNH.0000000000000908 -
Molecular Aspects of Medicine Feb 2024Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is... (Review)
Review
Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma.
Topics: Animals; Humans; Glaucoma, Open-Angle; Genome-Wide Association Study; Genetic Predisposition to Disease; Glaucoma; Genotype
PubMed: 38039744
DOI: 10.1016/j.mam.2023.101229 -
European Journal of Neurology Jul 2023Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and the risk of amyotrophic lateral sclerosis (ALS),...
OBJECTIVE
Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and the risk of amyotrophic lateral sclerosis (ALS), potentially prone to bias. Therefore, we aimed to study whether lipid metabolism involves genetically determined risk factors for ALS through Mendelian randomization (MR) analysis.
METHODS
Using genome-wide association study summary-level data for total cholesterol (TC) (n = 188,578), high-density lipoprotein cholesterol (HDL-C) (n = 403,943), low-density lipoprotein cholesterol (LDL-C) (n = 440,546), apolipoprotein A1 (ApoA1) (n = 391,193), apolipoprotein B (ApoB) (n = 439,214), and ALS (12,577 cases and 23,475 controls), we implemented a bidirectional MR study to evaluate a genetic relation between lipids and ALS risk. We performed a mediation analysis to assess whether LDL-C is a potential mediator on the pathway from traits of LDL-C-related polyunsaturated fatty acids (PUFAs) to ALS risk.
RESULTS
We identified genetically predicted increased lipid levels to be associated with the risk of ALS, whereby elevated LDL-C had the most potent effect (OR 1.028, 95% CI 1.008-1.049, p = 0.006). The effect of increased levels of apolipoproteins on ALS was similar to their corresponding lipoproteins. ALS did not cause any changes in lipid levels. We found no relation between LDL-C-modifying lifestyles and ALS. The mediation analysis revealed that LDL-C could act as an active mediator for linoleic acid, with the mediation effect estimated to be 0.009.
CONCLUSIONS
We provided high-level genetic evidence verifying the positive link between preclinically elevated lipid and ALS risk that had been described in previous genetic and observational studies. We also demonstrated the mediating role of LDL-C in the pathway from PUFAs to ALS.
Topics: Humans; Amyotrophic Lateral Sclerosis; Cholesterol, LDL; Mendelian Randomization Analysis; Genome-Wide Association Study; Risk Factors; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 36999624
DOI: 10.1111/ene.15810 -
Nutrients Aug 2023This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed,... (Review)
Review
This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed, Embase, and Web of Science databases were searched using the keywords 'fatty acid' and 'sarcopenia'. Results: A total of 14 clinical and 11 pre-clinical (including cell and animal studies) studies were included. Of the 14 clinical studies, 12 used omega-3 polyunsaturated fatty acids (PUFAs) as supplements, 1 study used ALA and 1 study used CLA. Seven studies combined the use of fatty acid with resistant exercises. Fatty acids were found to have a positive effect in eight studies and they had no significant outcome in six studies. The seven studies that incorporated exercise found that fatty acids had a better impact on elderlies. Four animal studies used novel fatty acids including eicosapentaenoic acid, trans-fatty acid, and olive leaf extraction as interventions. Three animal and four cell experiment studies revealed the possible mechanisms of how fatty acids affect muscles by improving regenerative capacity, reducing oxidative stress, mitochondrial and peroxisomal dysfunctions, and attenuating cell death. Conclusion: Fatty acids have proven their value in improving sarcopenia in pre-clinical experiments. However, current clinical studies show controversial results for its role on muscle, and thus the mechanisms need to be studied further. In the future, more well-designed randomized controlled trials are required to assess the effectiveness of using fatty acids in humans.
Topics: Animals; Humans; Muscles; Cell Death; Databases, Factual; Dietary Supplements; Eicosapentaenoic Acid; Fatty Acids; Sarcopenia
PubMed: 37630803
DOI: 10.3390/nu15163613 -
Medicinal Research Reviews Sep 2023The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID-19 pandemic witnessed... (Review)
Review
The global burden of respiratory diseases is enormous, with many millions of people suffering and dying prematurely every year. The global COVID-19 pandemic witnessed recently, along with increased air pollution and wildfire events, increases the urgency of identifying the most effective therapeutic measures to combat these diseases even further. Despite increasing expenditure and extensive collaborative efforts to identify and develop the most effective and safe treatments, the failure rates of drugs evaluated in human clinical trials are high. To reverse these trends and minimize the cost of drug development, ineffective drug candidates must be eliminated as early as possible by employing new, efficient, and accurate preclinical screening approaches. Animal models have been the mainstay of pulmonary research as they recapitulate the complex physiological processes, Multiorgan interplay, disease phenotypes of disease, and the pharmacokinetic behavior of drugs. Recently, the use of advanced culture technologies such as organoids and lung-on-a-chip models has gained increasing attention because of their potential to reproduce human diseased states and physiology, with clinically relevant responses to drugs and toxins. This review provides an overview of different animal models for studying respiratory diseases and evaluating drugs. We also highlight recent progress in cell culture technologies to advance integrated models and discuss current challenges and present future perspectives.
Topics: Animals; Humans; Pandemics; COVID-19; Drug Development
PubMed: 37119028
DOI: 10.1002/med.21956 -
Journal of Cosmetic Dermatology Dec 2023There is an increasing demand for facial skin rejuvenation. Specialized aesthetic skincare treatments may be one of the first steps to help prevent or treat facial signs... (Review)
Review
BACKGROUND
There is an increasing demand for facial skin rejuvenation. Specialized aesthetic skincare treatments may be one of the first steps to help prevent or treat facial signs of aging. This article discusses aesthetic skin care for facial skin rejuvenation, particularly data on two creams containing Macrocystis pyrifera ferment.
METHODS
The authors convened a dermatology advisory board to discuss challenges and practices in using skincare for facial rejuvenation, combining their expert opinion and experience on facial rejuvenation with preclinical and clinical data on two creams containing Macrocystis pyrifera ferment and a review of the literature.
RESULTS
Preclinical and clinical studies on Macrocystis pyrifera ferment and two creams containing the ferment exhibit anti-inflammatory, anti-aging, and healing properties. In preclinical studies, the ferment demonstrated collagen type I enhancing properties in ex vivo skin models, and skin cells treated with the ferment migrated faster than untreated cells in the in vitro study. In clinical studies measuring visible anti-inflammatory activity, the ferment alone and the ferment-containing products significantly decreased erythema, and in anti-aging studies, they improved visible skin aging parameters. Finally, in clinical studies on the stratum corneum, the two creams increased moisture levels and decreased transepidermal water loss (TEWL), reflecting healing by enhancing barrier strength and recovery.
CONCLUSIONS
The Macrocystis pyrifera ferment and creams containing the ferment are effective skin care treatment products to decrease the visible effects of inflammation and signs of aging while promoting healing by enhancing barrier resilience and recovery.
Topics: Humans; Macrocystis; Rejuvenation; Skin; Epidermis; Dermatologic Agents; Skin Aging; Anti-Inflammatory Agents
PubMed: 38041526
DOI: 10.1111/jocd.15986 -
World Journal of Oncology Apr 2024Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step... (Review)
Review
Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step forward in translatability of pigs as a biomedical model for various human diseases. Similarities between humans and pigs in terms of anatomy, physiology, genetics, and immunology have allowed pigs to become a comprehensive preclinical model for human diseases. With a diverse range, from craniofacial and ophthalmology to reproduction, wound healing, musculoskeletal, and cancer, pigs have provided a seminal understanding of human pathophysiology. This review focuses on the current research using pigs as preclinical models for cancer research and highlights the strengths and opportunities for studying various human cancers.
PubMed: 38545477
DOI: 10.14740/wjon1763