Present Review Research Articles

Decoding long non‑coding RNAs: Friends and foes in cancer development (Review).

Cancer remains a formidable adversary, challenging medical advancements with its dismal prognosis, low cure rates and high mortality rates. Within this intricate landscape, long non‑coding RNAs (lncRNAs) emerge as pivotal players, orchestrating proliferation and migration of cancer cells. Harnessing the potential of lncRNAs as therapeutic targets and prognostic markers holds immense promise. The present comprehensive review delved into the molecular mechanisms underlying the involvement of lncRNAs in the onset and progression of the top five types of cancer. By meticulously examining lncRNAs across diverse types of cancer, it also uncovered their distinctive roles, highlighting their exclusive oncogenic effects or tumor suppressor properties. Notably, certain lncRNAs demonstrate diverse functions across different cancers, confounding the conventional understanding of their roles. Furthermore, the present study identified lncRNAs exhibiting aberrant expression patterns in numerous types of cancer, presenting them as potential indicators for cancer screening and diagnosis. Conversely, a subset of lncRNAs manifests tissue‑specific expression, hinting at their specialized nature and untapped significance in diagnosing and treating specific types of cancer. The present comprehensive review not only shed light on the intricate network of lncRNAs but also paved the way for further research and clinical applications. The unraveled molecular mechanisms offer a promising avenue for targeted therapeutics and personalized medicine, combating cancer proliferation, invasion and metastasis.

Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

ω‑3 fatty acids in atherosclerotic cardiovascular disease (Review).

Atherosclerotic cardiovascular disease (ASCVD) is one of the most common chronic diseases in the world. Epidemiological evidence and clinical trials have shown that ω-3 fatty acids have a variety of promoting effects in reducing the risk of ASCVD, but different conclusions of large randomized controlled trials make their clinical use in the prevention and treatment of ASCVD controversial. The present review focuses on the pharmacological mechanism, clinical trials and evidence value of clinical applications of ω-3 fatty acids in order to provide theoretical and practical evidence for the clinical application strategy, and follow-up research and development of ω-3 fatty acids as anti-ASCVD drugs.

Traditional Therapies Involving Nutrition for the Management of COVID-19

Abstract: The novel coronavirus SARS-CoV-2 causes ARDS, respiratory failure, organ failure, and even death. The immunopathology associated with the SARS-CoV-2 virus involves an overproduction of pro-inflammatory cytokines, commonly referred to as a "cytokine storm." SARS-CoV-2 is a positive-sense RNA virus responsible for the COVID-19 pandemic. The pandemic kept the world silent since its emergence by engulfing most public activities. The symptoms of COVID-19 like coughing, fatigue, dysphagia, and poor appetite reduce the nutritional intake among the patients. Therefore, the nutritional status of the infected patients needs monitoring. The deficiency of nutrition puts the patients at high risk during clinical therapy. Moreover, insufficient micronutrients lead to weakened immune responses, causing improper cytokine secretion, changes in secretory antibody response, and reduced antibody affinity; all of which enhance the vulnerability of viral infections. As the pandemic is affecting a large number of people all over the world, there is an urgent requirement for newer therapies/therapeutics with nutritional information for hospitalized and recovered patients of COVID-19. Hospitalized patients are highly at risk of malnutrition, weight loss, muscle loss, etc. Therefore, nutritional support is essential for COVID-19 patients. Based on the recent reports obtained from the COVID-19 resources; the present review describes the various clinical therapies, the involvement of nutritional support, the role of diet, the modified lifestyle, and micronutrients (zinc, selenium, and vitamin D) in the management of COVID-19 patients.

Emerging concepts of myosin 18A isoform mechanobiology in organismal and immune system physiology, development, and function.

Alternative and combinatorial splicing of myosin 18A (MYO18A) gene transcripts results in expression of MYO18A protein isoforms and isoform variants with different membrane and subcellular localizations, and functional properties. MYO18A proteins are members of the myosin superfamily consisting of a myosin-like motor domain, an IQ motif, and a coiled-coil domain. MYO18A isoforms, however, lack the ability to hydrolyze ATP and do not perform ATP-dependent motor activity. MYO18A isoforms are distinguished by different amino- and carboxy-terminal extensions and domains. The domain organization and functions of MYO18Aα, MYO18Aβ, and MYO18Aγ have been studied experimentally. MYO18Aα and MYO18Aβ have a common carboxy-terminal extension but differ by the presence or absence of an amino-terminal KE repeat and PDZ domain, respectively. The amino- and carboxy-terminal extensions of MYO18Aγ contain unique proline and serine-rich domains. Computationally predicted MYO18Aε and MYO18Aδ isoforms contain the carboxy-terminal serine-rich extension but differ by the presence or absence of the amino-terminal KE/PDZ extension. Additional isoform variants within each category arise by alternative utilization or inclusion/exclusion of small exons. MYO18Aα variants are expressed in somatic cells and mature immune cells, whereas MYO18Aβ variants occur mainly in myeloid and natural killer cells. MYO18Aγ expression is selective to cardiac and skeletal muscle. In the present review perspective, we discuss current and emerging concepts of the functional specialization of MYO18A proteins in membrane and cytoskeletal dynamics, cellular communication and signaling, endocytic and exocytic organelle movement, viral infection, and as the SP-R210 receptor for surfactant protein A.

A REVIEW ON FAST DISSOLVING FILM

Orally fast dissolving films (OFDFs) have been introduced in the market recently as they provide convenience and ease of use over other dosage forms such as orally disintegrating tablets. This technology evolved over the past few years from the confection and oral care markets in the form of breath strips and became a novel and widely accepted form by consumers, so OFDFs are gaining the interest of large number of pharmaceutical industries. Orally fast dissolving film is the type of drug delivery system which when placed in the oral cavity, disintegrate or dissolve within few seconds without the intake of water. OFDFs are very similar to postage stamp in their shape, size and thickness. These films have a potential to deliver the drug systemically through intragastric, sublingual or buccal route of administration and also has been used for local action. This type of technology offer a convenient way of dosing medication, not to special population groups like pediatric, geriatric, bedridden patients, mentally ill patients, but also to the general population. The present review provides an account of various formulation considerations, method of preparation and quality control of the OFDFs.

GEOGRAPHICAL DESCRIPTION AND PHARMACOLOGICAL PROPERTIES OF DICHANTHIUM ANNULATUM: A REVIEW

Dichanthium annulatum herb belongs to Poaceae family; also referred to as marvel grass. It grows to a height of about 25cm. Due to its straightforward and affordable development from seed, it is used as forage. The present review was based on the geographical description and pharmacological properties of dichanthium annulatum. It is indigenous to regions of Africa, the Middle East, and tropical Asia. It has been brought to many different regions of the world for cultivation, and in some, like Australia, it has established itself as a native species. This pasture grass is well-liked in various regions. It can be harvested for hay and silage and used in fields to graze livestock. It can grow in a wide range of soil types, including those with a lot of clay and sand, poor drainage, and a little saline and alkaline soil. It creates turf that can withstand pressure from grazing animals. It can bounce back from fire and drought, but it can't stand frost and shade as well. Although it doesn't need fertiliser, it does benefit from a little more nitrogen. It concluded that D. annulatum is versatile herb having diverse pharmacological activities including antioxidant, antioxidant activity index, DNA damage protection assay, antimicrobial assay, and cytotoxic activity. It also reported for protective effect against DNA damage. These biological properties are reported due to numerous phytochemicals present in the D. annulatum herb.

Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents: A narrative review.

Glaucoma, an irreversible optic neuropathy, primarily affects retinal ganglion cells (RGC) and causes vision loss and blindness. The damage to RGCs in glaucoma occurs by various mechanisms, including elevated intraocular pressure, oxidative stress, inflammation, and other neurodegenerative processes. As the disease progresses, the loss of RGCs leads to vision loss. Therefore, protecting RGCs from damage and promoting their survival are important goals in managing glaucoma. In this regard, resveratrol (RES), a polyphenolic phytoalexin, exerts antioxidant effects and slows down the evolution and progression of glaucoma. The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina. Additionally, RES plays protective roles in RGCs by promoting cell growth, reducing apoptosis, and decreasing oxidative stress in H2O2-exposed RGCs. RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways. RES could alleviate retinal function impairment by suppressing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway. Therefore, RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

Liquid-phase NMR of asphaltenes.

The present review focuses on the most recent advances in liquid-phase NMR of asphaltenes, leaving apart an overwhelming amount of publications dealing with solid-state NMR investigations in this field. Owing to the complexity of the coal-derived products, and in particular, asphaltenes, their 1H and 13C NMR spectra consist of a number of overlapping signals belonging to different hydrocarbon types. Comprehensive studies of asphaltenes by means of NMR reveal the characteristic functional groups of their fractions together with the spectral regions in which they resonate. NMR studies of asphaltenes provide a straightforward guideline for their chemical composition and that of the related coal-derived products.

Recent Insights into the Antimicrobial Properties of Phyllanthus emblica L.: A Comprehensive Review of Wonder Berry.

Phyllanthus emblica L., or Amla, is known for its therapeutic properties and has been used as a medicinal plant. It is rich in vitamin C and other bioactive phytochemicals like polyphenols, gallic acid, chebulagic acid, leutolin, quercetin, etc. Different parts of this plant are used to treat various viral, bacterial, and fungal diseases. This review article summarizes the recent literature relevant to the antiviral, antibacterial, and antifungal effects of P. emblica. A variety of bacteria (Staphylococcus aureus, Bacillus subtillus, Enterococcus faecalis, Salmonella typhi, and Escherichia, etc.), fungi (Alternaria alternate Botroyodiplodia theobromae, Colletotrichum corcori, Curvularia lunata, Fusarium exquisite, Fusarium solanii, Aspergillus niger, Candida albicans, Colletotrichum gleosparoitis, and Macrophomina phaseolina) and viruses, like Influenza A virus strain H3N2, hepatitis B, Human Immunodeficiency virus type-1 (HIV-1), Simplex virus type 1 (HSV-1) and type 2 (HSV-2) have experimented. Different techniques were used based on the way of identification. `For example, disc diffusion, dilution methods, sound diffusion, Immuno-peroxidase monolayer assay, serum HBV and HBsAg assay, enzyme immunoassay, etc. The present review analyzed and summarized the antimicrobial activities of P. emblica and possible mechanisms of action to provide future directions in translating these findings clinically.

A bibliometric analysis of Quality 4.0: current status, trends and future research directions

PurposeThis review paper aims to explore and investigate the Quality 4.0 current knowledge, emerging areas, and trends available in the literature and provide insights for future research directions. The bibliometric analysis determines the most prominent journals, authors, countries, articles, and themes. The Citation and PageRank analysis identifies the most influential and prestigious articles. The author's keyword analysis identifies the research theme, patterns, and trends within a particular area of research.Design/methodology/approachThis study utilised the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) declaration as a review protocol, and the data is retrieved accordingly. Therefore, 104 articles from Scopus and 28 from Web of Science were combined in R-Environment, and 25 duplicates were removed using RStudio. Finally, 107 papers were selected for further analysis. After the abstract level screening, the study reviewed 99 articles bibliographically published in peer-reviewed journals from prominent academic databases Scopus and WoS between 2011 to April 2023. We used the VOSviewer software tool for analysing bibliometric networks that allow the construction, visualisation, and exploration of maps based on any form of network data.FindingsThe review identified emerging themes: artificial intelligence, digitalization, sustainability, root cause analysis, topic modelling, and digital voice-of-customers. To establish the intellectual structure of the field and identify gaps, co-citation and content analysis were used. The content of 49 papers in the identified clusters was then carefully analysed. The four primary themes are the relationship of Quality 4.0 with Industry 4.0, the conceptualization of Quality 4.0, recommendations for the new Quality 4.0 model, and the impact of Quality 4.0. The findings provide an excellent foundation for future research in this field for policymakers, managers, practitioners, and academia.Originality/valueThis is the first systematic literature review-cum-bibliometric analysis on quality 4.0 that covers the field comprehensively. Based on the present review, the paper proposes six possible future research directions to investigate.

Omega-3 Supplementation and Its Effects on Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The progression of OA is multifactorial and is influenced by the underlying cause of inflammation, which includes but is not limited to trauma, metabolism, biology, comorbidities, and biomechanics. Although articular cartilage is the main tissue affected in osteoarthritis, the chronic inflammatory environment negatively influences the surrounding synovium, ligaments, and subchondral bone, further limiting their functional abilities and enhancing symptoms of OA. Treatment for osteoarthritis remains inconsistent due to the inability to determine the underlying mechanism of disease onset, severity of symptoms, and complicating comorbidities. In recent years, diet and nutritional supplements have gained interest regarding slowing the disease process, prevention, and treatment of OA. This is due to their anti-inflammatory properties, which result in a positive influence on pain, joint mobility, and cartilage formation. More specifically, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways. The present review is focused on the assessment of evidence explaining the inflammatory processes of osteoarthritis and the influence of omega-3 supplementation to modulate the progression of osteoarthritis.

High‐Precision Dilatometry for the Study of Precipitation Processes and Microalloying Effects in Lightweight Alloys ‐ A Specific Review

By dilatometry, the absolute change in the length of a sample is measured. As length, i.e., volume, is a state variable, its change can be monitored for long time ranges. This is the decisive advantage compared to the widely applied calorimetric methods which are based on a rate (change of heat) and where the maximum time range is determined by the resolution limit of the heat flow measurement. In contrast, if the measurement environment is kept at a constant temperature, dilatometric signals can be measured for very long time ranges down to very small changes with resolution in the nm range. The application of high‐stability isothermal dilatometry for studying precipitation phenomena in Al(Mg,Si)‐, Ti(V)‐, and Ti(Cr)‐alloys is summarized in the present review. Al(Mg,Si) turns out as a prime example where the various phases can unambiguously be distinguished by their characteristic length change features. For Ti(V), the influence of the oxygen impurity on the omega phase formation, and for Ti(Cr), the effect of Sn alloying on the omega phase formation can be revealed by dilatometry. The results on Al(Mg, Si) are compared with dilatometry on Al(Cu)‐alloys upon time‐linear heating, for which also the effect of microalloying with Au is studied.

Comparison of Immediate Implantation into the Socket with and without Periapical Pathology: Systematic Review and Meta-Analysis

Background and Objectives: The present systematic review and meta-analysis were conducted to evaluate and compare the long-term clinical outcomes of immediate implants placed into fresh sockets with and without periapical pathology. Materials and Methods: After the search and review of the literature in the electronic databases, 109 publications were achieved. The titles and abstracts of 66 publications were screened. After the evaluation of the full text of 22 publications, based on the inclusion criteria, six controlled clinical studies were included in this systematic review and meta-analysis. Results: The statistical calculation showed no heterogeneity among the studies included. The implant survival was 99.6% in the test (socket with periapical pathology) and control (socket without periapical pathology) groups of all the clinical trials. The results of the meta-analysis showed no statistically significant difference between test and control groups regarding the marginal bone level and the width of keratinized mucosa in all the studies. Other parameters indicating plaque level, bleeding on probing, and gingival recession also did not differ between test and control groups at the final follow-up in nearly all studies. Conclusions: Within the limitation of this systemic review and meta-analysis, the obtained data suggest that implants immediately placed into the extraction sockets of teeth exhibiting periapical pathology can be successfully osseointegrated for an extended period.

Tumefactive Demyelinating Lesions: An Illustrative Pediatric Case With an Atypical Presentation and Literature Review

Tumefactive Demyelinating Lesions: An Illustrative Pediatric Case With an Atypical Presentation and Literature Review

Chemometric-based drug discovery approaches from natural origins using hyphenated chromatographic techniques.

Isolation and characterization of bioactive components from complex matrices of marine or terrestrial biological origins are the most challenging issues for natural product chemists. Biochemometric is a new potential scope in natural product analytical science, and it is a methodology to find the compound's correlation to their bioactivity with the help of hyphenated chromatographic techniques and chemometric tools. The present review aims to evaluate the application of chemometric tools coupled to chromatographic techniques for drug discovery from natural resources. The searching keywords "biochemometric," "chemometric," "chromatography," "natural products bioassay," and "bioassay" were selected to search the published articles between 2010-2023 using different search engines including "Pubmed", "Web of Science," "ScienceDirect," and "Google scholar." An initial stage in natural product analysis is applying the chromatographic hyphenated techniques in conjunction with biochemometric approaches. Among the applied chromatographic techniques, liquid chromatography (LC) techniques, have taken up more than half (53%) and also, mass spectroscopy (MS)-based chromatographic techniques such as LC-MS are the most widely used techniques applied in combination with chemometric methods for natural products bioassay. Considering the complexity of dataset achieved from chromatographic hyphenated techniques, chemometric tools have been increasingly employed for phytochemical studies in the context of determining botanicals geographical origin, quality control, and detection of bioactive compounds. Biochemometric application is expected to be further improved with advancing in data acquisition methods, new efficient preprocessing, model validation and variable selection methods which would guarantee that the applied model to have good prediction ability in compound relation to its bioactivity.

Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.

Enhancing AI Research for Breast Cancer: A Comprehensive Review of Tumor-Infiltrating Lymphocyte Datasets.

The field of immunology is fundamental to our understanding of the intricate dynamics of the tumor microenvironment. In particular, tumor-infiltrating lymphocyte (TIL) assessment emerges as essential aspect in breast cancer cases. To gain comprehensive insights, the quantification of TILs through computer-assisted pathology (CAP) tools has become a prominent approach, employing advanced artificial intelligence models based on deep learning techniques. The successful recognition of TILs requires the models to be trained, a process that demands access to annotated datasets. Unfortunately, this task is hampered not only by the scarcity of such datasets, but also by the time-consuming nature of the annotation phase required to create them. Our review endeavors to examine publicly accessible datasets pertaining to the TIL domain and thereby become a valuable resource for the TIL community. The overall aim of the present review is thus to make it easier to train and validate current and upcoming CAP tools for TIL assessment by inspecting and evaluating existing publicly available online datasets.

Systematic review and meta-analysis of the incidence of incisional hernia in urological surgery.

To evaluate the incidence of incisional hernia in patients undergoing direct access to the abdominal cavity in urological surgery. We conducted a systematic review in Pubmed, Embase, and Cochrane Central from 1980 to the present according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Eighty-four studies were selected for inclusion in this analysis, and meta-analysis and meta-regression were performed. The total incidence in the 84 studies was 4.8% (95% CI 3.7% - 6.2%) I2 93.84%. Depending on the type of incision, it was higher in the open medial approach: 7.1% (95% CI 4.3%-11.8%) I2 92.45% and lower in laparoscopic surgery: 1.9% (95% CI 1%-3.4%) I2 71, 85% According to access, it was lower in retroperitoneal: 0.9% (95% CI 0.2%-4.8%) I2 76.96% and off-midline: 4.7% (95% CI 3.5%-6.4%) I2 91.59%. Regarding the location of the hernia, parastomal hernias were more frequent: 15.1% (95% CI 9.6% - 23%) I2 77.39%. Meta-regression shows a significant effect in reducing the proportion of hernias in open lateral, laparoscopic and hand-assisted compared to medial open access. The present review finds the access through the midline and stomas as the ones with the highest incidence of incisional hernia. The use of the lateral approach or minimally invasive techniques is preferable. More prospective studies are warranted to obtain the real incidence of incisional hernias and evaluate the role of better techniques to close the abdomen.

Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis

Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects.