Nigella sativa Oil-loaded Ethanolic Vesicular Gel for Imiquimod-induced Plaque Psoriasis: Physicochemical Characterization, Rheological Studies, and In vivo Efficacy.

BACKGROUND: The therapeutic effect of NS oil in mild to moderate psoriasis is limited owing to low play load of thymoquinone ( < 15 %w/w), irritation, dripping, low viscosity and thus, less contact time on the lesions. AIMS: This study aimed at developing and characterizing the ethanolic vesicular hydrogel system of Nigella sativa (NS) oil (NS EV hydrogel) for the enhancement of anti-psoriatic activity. OBJECTIVE: The objective of this study was to develop NS EV hydrogel and evaluate its anti-psoriatic activity. METHODS: The identification and quantification of TQ content in different NS seed extracts and marketed oil were measured by an HPTLC method using n-hexane and ethyl acetate as solvent systems. Preparation of ethanolic vesicles (EVs) was performed by solvent injection method, while its antipsoriatic activity was evaluated employing an Imiquad (IMQ)-induced plaque psoriasis animal model. RESULTS: A compact HPTLC band was obtained for TQ at an Rf value of 0.651. The calibration plot was linear in the range of 1-10 µg/spot, and the correlation coefficient of 0.990 was indicative of good linear dependence of peak area on concentration. From the different NS sources, the high TQ content was obtained in the marketed cold press oil, i.e., 1.45±0.08mg/ml. Out of various NS oilloaded EVs, the F6 formulation revealed the smallest particle size (278.1nm), with log-normal size distribution (0.459) and adequate entrapment efficiency. A non-uniform shape was observed in the transmission electron microscopy. The viscosity of F6 formulation hydrogel was 32.34 (Pa·s), which exhibited plastic behavior. In vivo, efficacy studies demonstrated decreased inflammation of the epidermis and dermis and a marked decrease in the levels of IL-17 by NS EV hydrogel compared to plain NS oil and standard drugs (Betamethasone and Dr. JRK Psorolin Oil). CONCLUSION: It may be concluded from the findings that NS-loaded EV gel was as good as betamethasone cream but more efficacious than the other treatments.

Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation.

Mitochondrial ribosomes (mitoribosomes) have undergone substantial evolutionary structural remodeling accompanied by loss of ribosomal RNA, while acquiring unique protein subunits located on the periphery. We generated CRISPR-mediated knockouts of all 14 unique (mitochondria-specific/supernumerary) human mitoribosomal proteins (snMRPs) in the small subunit to study the effect on mitoribosome assembly and protein synthesis, each leading to a unique mitoribosome assembly defect with variable impact on mitochondrial protein synthesis. Surprisingly, the stability of mS37 was reduced in all our snMRP knockouts of the small and large ribosomal subunits and patient-derived lines with mitoribosome assembly defects. A redox-regulated CX9C motif in mS37 was essential for protein stability, suggesting a potential mechanism to regulate mitochondrial protein synthesis. Together, our findings support a modular assembly of the human mitochondrial small ribosomal subunit mediated by essential supernumerary subunits and identify a redox regulatory role involving mS37 in mitochondrial protein synthesis in health and disease.

Expanding Arsenal against Ocular Diseases through Nanoemulsion: Success So Far and the Road Ahead.

The eye is a most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. In the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos which provides increased permeation ability and ocular bioavailability which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Nanoemulsions (NEs) over the past decade have been used to treat several ocular diseases in the anterior eye segment. This review summarizes the economic burden, pathology of ocular diseases, formulation considerations for ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery highlighting their performance in pre-clinical studies.

Non-coding RNA: A key regulator in the Glutathione-GPX4 pathway of ferroptosis.

Ferroptosis, a form of regulated cell death, has emerged as a crucial process in diverse pathophysiological states, encompassing cancer, neurodegenerative ailments, and ischemia-reperfusion injury. The glutathione (GSH)-dependent lipid peroxidation pathway, chiefly governed by glutathione peroxidase 4 (GPX4), assumes an essential part in driving ferroptosis. GPX4, as the principal orchestrator of ferroptosis, has garnered significant attention across cancer, cardiovascular, and neuroscience domains over the past decade. Noteworthy investigations have elucidated the indispensable functions of ferroptosis in numerous diseases, including tumorigenesis, wherein robust ferroptosis within cells can impede tumor advancement. Recent research has underscored the complex regulatory role of non-coding RNAs (ncRNAs) in regulating the GSH-GPX4 network, thus influencing cellular susceptibility to ferroptosis. This exhaustive review endeavors to probe into the multifaceted processes by which ncRNAs control the GSH-GPX4 network in ferroptosis. Specifically, we delve into the functions of miRNAs, lncRNAs, and circRNAs in regulating GPX4 expression and impacting cellular susceptibility to ferroptosis. Moreover, we discuss the clinical implications of dysregulated interactions between ncRNAs and GPX4 in several conditions, underscoring their capacity as viable targets for therapeutic intervention. Additionally, the review explores emerging strategies aimed at targeting ncRNAs to modulate the GSH-GPX4 pathway and manipulate ferroptosis for therapeutic advantage. A comprehensive understanding of these intricate regulatory networks furnishes insights into innovative therapeutic avenues for diseases associated with perturbed ferroptosis, thereby laying the groundwork for therapeutic interventions targeting ncRNAs in ferroptosis-related pathological conditions.

Quercetin in Oncology: A Phytochemical with Immense Therapeutic Potential.

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers.

Innovative approaches to wound healing: insights into interactive dressings and future directions.

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.

Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling.

Immunoglobulins (Ig), which exist either as B-cell receptors (BCR) on the surface of B cells or as antibodies when secreted, play a key role in the recognition and response to antigenic threats. The capability to jointly characterize the BCR and antibody repertoire is crucial for understanding human adaptive immunity. From peripheral blood, bulk BCR sequencing (bulkBCR-seq) currently provides the highest sampling depth, single-cell BCR sequencing (scBCR-seq) allows for paired chain characterization, and antibody peptide sequencing by tandem mass spectrometry (Ab-seq) provides information on the composition of secreted antibodies in the serum. Yet, it has not been benchmarked to what extent the datasets generated by these three technologies overlap and complement each other. To address this question, we isolated peripheral blood B cells from healthy human donors and sequenced BCRs at bulk and single-cell levels, in addition to utilizing publicly available sequencing data. Integrated analysis was performed on these datasets, resolved by replicates and across individuals. Simultaneously, serum antibodies were isolated, digested with multiple proteases, and analyzed with Ab-seq. Systems immunology analysis showed high concordance in repertoire features between bulk and scBCR-seq within individuals, especially when replicates were utilized. In addition, Ab-seq identified clonotype-specific peptides using both bulk and scBCR-seq library references, demonstrating the feasibility of combining scBCR-seq and Ab-seq for reconstructing paired-chain Ig sequences from the serum antibody repertoire. Collectively, our work serves as a proof-of-principle for combining bulk sequencing, single-cell sequencing, and mass spectrometry as complementary methods towards capturing humoral immunity in its entirety.

Computational and biological approaches in repurposing ribavirin for lung cancer treatment: Unveiling antitumorigenic strategies.

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.

Ferroptosis and circular RNAs: new horizons in cancer therapy.

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. See also the graphical abstract(Fig. 1).

Fecal microbiome extract downregulates the expression of key proteins at the interface between airway remodelling and lung cancer pathogenesis in vitro.

Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.

Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance.

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.

Non-coding RNA mediated regulation of PI3K/Akt pathway in hepatocellular carcinoma: Therapeutic perspectives.

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

Treatment avenues for age-related macular degeneration: Breakthroughs and bottlenecks.

Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Harnessing the role of microneedles as sensors: current status and future perspectives.

In recent years, microneedles (MNs) have been transformed to serve a wide range of applications in the biomedical field. Their role as sensors in wearable devices has provided an alternative to blood-based monitoring of health and diagnostic methods. Hence, they have become a topic of research interest for several scientists working in the biomedical field. These MNs as sensors offer the continuous monitoring of biomarkers like glucose, nucleic acids, proteins, polysaccharides and electrolyte ions, which can therefore screen for and diagnose disease conditions in humans. The present review focuses on types of MN sensors and their applications. Various clinical trials and bottlenecks of MN R&D are also discussed.

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead.

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.

Exploring the complex interplay between Parkinson's disease and BAG proteins.

Parkinsons disease (PD) is a chronic fast growing neurodegenerative disorder of Central Nervous System (CNS) characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and formation of Lewy bodies (LBs) which causes dopamine deficiency within basal ganglia leading to motor and non-motor manifestation. According to reports, many factors are responsible for pathogenesis of PD which includes environmental factors, genetic factors, and aging factors. Whereas death of dopaminergic neurons is also caused by oxidative stress, neuroinflammation, and autophagy disorder. Molecular chaperones/co-chaperones are proteins that binds to an unstable conformer of another protein and stabilizes it. Chaperones prevent incorrect interaction between non-native polypeptides which increases the yield but not the rate of reaction. The Bcl-2-associated athanogene (BAG) is a multifunctional group of proteins belonging to BAG family of co-chaperones. Recent studies demonstrates that chaperones interact with PD-related proteins. Co-chaperones like BAG family proteins regulate the function of chaperones. Molecular chaperones regulate the mitochondrial functions by interacting with the PD-related proteins associated with it. This review studies the contribution of chaperones and PD-related proteins in pathogenesis of PD aiming to provide an alternate molecular target for preventing the disease progression.

Exploring the role of the ocular surface in the lung-eye axis: Insights into respiratory disease pathogenesis.

Chronic respiratory diseases (CRDs) represent a significant proportion of global health burden, with a wide spectrum of varying, heterogenic conditions largely affecting the pulmonary system. Recent advances in immunology and respiratory biology have highlighted the systemic impact of these diseases, notably through the elucidation of the lung-eye axis. The current review focusses on understanding the pivotal role of the lung-eye axis in the pathogenesis and progression of chronic respiratory infections and diseases. Existing literature published on the immunological crosstalk between the eye and the lung has been reviewed. The various roles of the ocular microbiome in lung health are also explored, examining the eye as a gateway for respiratory virus transmission, and assessing the impact of environmental irritants on both ocular and respiratory systems. This novel concept emphasizes a bidirectional relationship between respiratory and ocular health, suggesting that respiratory diseases may influence ocular conditions and vice versa, whereby this conception provides a comprehensive framework for understanding the intricate axis connecting both respiratory and ocular health. These aspects underscore the need for an integrative approach in the management of chronic respiratory diseases. Future research should further elucidate the in-depth molecular mechanisms affecting this axis which would pave the path for novel diagnostics and effective therapeutic strategies.