Specific Organs Research Articles

Artificial Intelligence in Pharmaceutical Industry: Revolutionizing Drug Development and Delivery

Abstract: Artificial Intelligence (AI) has ushered in a profound revolution within the pharmaceutical sector, effectively streamlining the processes of drug development and delivery. The application of AI-driven tools and methodologies, including machine learning and natural language processing, in the realm of pharmaceutical research and development has yielded recent breakthroughs. This accelerated the drug discovery process by meticulously scrutinizing copious data and pinpointing potential drug targets, as expounded upon in this comprehensive review. Furthermore, AI has found utility in optimizing clinical trials, thereby refining trial designs and cost-effectiveness and bolstering patient safety. Notably, AI-based strategies are being harnessed to enhance drug delivery, fostering the creation of intelligent drug delivery systems engineered to target specific cells or organs. This results in heightened efficacy and a concomitant reduction in undesirable side effects. This review also delves into the potential biases residing within AI algorithms and the challenges associated with data quality when integrating AI into the pharmaceutical sphere. The findings of this study underscore the immense potential of artificial intelligence in reshaping the pharmaceutical industry, thereby enhancing the quality of life for patients worldwide.

Nano-radiopharmaceuticals as therapeutic agents.

In recent years, there has been an increased interest in exploring the potential synergy between nanotechnology and nuclear medicine. The application of radioactive isotopes, commonly referred to as radiopharmaceuticals, is recognized in nuclear medicine for diagnosing and treating various diseases. Unlike conventional pharmaceutical agents, radiopharmaceuticals are designed to work without any pharmacological impact on the body. Nevertheless, the radiation dosage employed in radiopharmaceuticals is often sufficiently high to elicit adverse effects associated with radiation exposure. Exploiting their capacity for selective accumulation on specific organ targets, radiopharmaceuticals have utility in treating diverse disorders. The incorporation of nanosystems may additionally augment the targeting capability of radiopharmaceuticals, leveraging their distinct pharmacokinetic characteristics. Conversely, radionuclides could be used in research to assess nanosystems pharmacologically. However, more investigation is needed to verify the safety and effectiveness of radiopharmaceutical applications mediated by nanosystems. The use of nano-radiopharmaceuticals as therapeutic agents to treat various illnesses and disorders is majorly covered in this review. The targeted approach to cancer therapy and various types of nanotools for nano-radiopharmaceutical delivery, is also covered in this article.

Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions.

Lipid nanoparticles (LNPs) have become the dominant drug delivery technology in industry, holding the promise to deliver RNA to up or down-regulate any protein of interest. LNPs have mostly been targeted to specific cell types or organs by physicochemical targeting in which LNP's lipid compositions are adjusted to find mixtures with the desired tropism. Here lung-tropic LNPs are examined, whose organ tropism derives from containing either a cationic or ionizable lipid conferring a positive zeta potential. Surprisingly, these LNPs are found to induce massive thrombosis. Such thrombosis is shown in the lungs and other organs, and it is shown that it is greatly exacerbated by pre-existing inflammation. This clotting is induced by a variety of formulations with cationic lipids, including LNPs and non-LNP nanoparticles, and even by lung-tropic ionizable lipids that do not have a permanent cationic charge. The mechanism depends on the LNPs binding to and then changing the conformation of fibrinogen, which then activates platelets and thrombin. Based on these mechanisms, multiple solutions are engineered that enable positively charged LNPs to target the lungs while ameliorating thrombosis. The findings illustrate how physicochemical targeting approaches must be investigated early for risks and re-engineered with a careful understanding of biological mechanisms.

Autophagy differentially regulates tissue tolerance of distinct target organs in graft-versus-host disease models.

Tissue-intrinsic mechanisms that regulate severity of systemic pathogenic immune-mediated diseases, such as acute graft-versus-host disease (GVHD), remain poorly understood. Following allogeneic hematopoietic stem cell transplantation, autophagy, a cellular stress protective response, is induced in host nonhematopoietic cells. To systematically address the role of autophagy in various host nonhematopoietic tissues, both specific classical target organs of acute GVHD (intestines, liver, and skin) and organs conventionally not known to be targets of GVHD (kidneys and heart), we generated mice with organ-specific knockout of autophagy related 5 (ATG5) to specifically and exclusively inhibit autophagy in the specific organs. When compared with wild-type recipients, animals that lacked ATG5 in the gastrointestinal tract or liver showed significantly greater tissue injury and mortality, while autophagy deficiency in the skin, kidneys, or heart did not affect mortality. Treatment with the systemic autophagy inducer sirolimus only partially mitigated GVHD mortality in intestine-specific autophagy-deficient hosts. Deficiency of autophagy increased MHC class I on the target intestinal epithelial cells, resulting in greater susceptibility to damage by alloreactive T cells. Thus, autophagy is a critical cell-intrinsic protective response that promotes tissue tolerance and regulates GVHD severity.

Expression of IZUMO1 and JUNO in the gonads of domestic cats (Felis catus)

Because of the time-consuming nature of surgical neutering and the rapid rate of reproduction among domestic cats, it is crucial to investigate alternative, nonsurgical methods of contraception for this species. Sperm protein IZUMO1 and its oocyte receptor JUNO have been proposed as potential targets for nonsurgical contraceptives. This study aimed to demonstrate (1) the protein coding sequence of feline IZUMO1 and JUNO, (2) gene expression in specific organs by measuring mRNA levels in different visceral tissues, and (3) the expression of IZUMO1 and JUNO during sperm maturation and folliculogenesis, respectively. Amplification for sequencing of feline IZUMO1 and JUNO was performed using the RT-PCR method. Levels of gene expression in different tissues were evaluated using real-time PCR. In situ hybridization was performed to localize JUNO mRNA in ovarian tissues. The complete coding sequences of IZUMO1 and JUNO were obtained and analyzed. A comparison between protein orthologs demonstrated the conservation of IZUMO1 and JUNO in Felidae. The real-time PCR results from various visceral organs indicated that IZUMO1 was significantly higher in the testis than in other organs, whereas JUNO was significantly higher in the ovary than in other organs. Expression of IZUMO1 was found to be higher in the testes than in the caput, corpus, and cauda of epididymides. In situ hybridization revealed that JUNO mRNA was in the ooplasm and nucleus of the primordial, primary, secondary, and antral follicles. Importantly, this was the first study to demonstrate the IZUMO1 and JUNO genes in the testis and ovary of cats. The results are useful for future research related to these genes and for developing contraceptives against these targets.

Nutrient Dynamics in a Coupled Terrestrial Biosphere and Land Model (ELM‐FATES‐CNP)

AbstractWe present a representation of nitrogen and phosphorus cycling in the Functionally Assembled Terrestrial Ecosystem Simulator, a demographic vegetation model within the Energy Exascale Earth System land model. This representation is modular, and designed to allow testing of multiple hypothetical approaches for carbon‐nutrient coupling in plants. Novel model hypotheses introduced in this work include, (a) the controls on plant acquisition of aqueous mineralized nutrients in the soil and (b) fairly straight forward methods of allocating nutrients to specific plant organs and their losses through live plant turnover as well as litter fluxes generated through plant mortality. This combines the new with pre‐existing hypotheses (such as nitrogen fixation and soil decomposition) into a system that can accommodate plant‐soil dynamics for a large number of size‐ and functional‐type‐resolved plant cohorts within a time‐since‐disturbance‐resolved ecosystem. Root uptake of nutrients is governed by fine root biomass, and plants vary in their fine root biomass allocation in order to balance carbon and nutrient limitations to growth. We test the sensitivity of the model to a wide range of parameter variations and structural representations, and in the context of observations at Barro Colorado Island, Panama. A key model prediction is that plants in the high‐light‐availability canopy positions allocate more carbon to fine roots than plants in low‐light understory environments, given the widely different carbon versus nutrient constraints of these two niches within a given ecosystem. This model provides a basis for exploring carbon‐nutrient coupling with vegetation demography within Earth system models.

Adult-Onset Still's Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options.

Adult-onset Still's disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. The disease may develop in both children and adults with overlapping clinical features, and although several subsets depending on the clinical manifestations and the cytokines expressed have been identified, the dichotomy between systemic juvenile idiopathic arthritis (sJIA) and AOSD nowadays has been overcome, and the pathology is considered a disease continuum between ages. Various therapeutic approaches have been evaluated thus far, and different compounds are under assessment for AOSD treatment. Historically, glucocorticoids have been employed for treating systemic manifestations of Still's disease, while conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) demonstrated efficacy in controlling the articular manifestations. Currently, biological (b) DMARDs are widely employed; IL-1 inhibitors such as anakinra and canakinumab have proven to have high efficacy and an excellent safety profile and the anti-IL-6 tocilizumab is approved for sJIA, with several trials and longitudinal studies confirming its efficacy and safety. Moreover, in the light of the 'window of opportunity', new evidence showed that the earlier these treatments are initiated, the sooner clinical inactivity can be achieved. Other treatment options are being considered since several molecules involved in the disease pathophysiology can be targeted through various mechanisms. This review will provide a broad overview of AOSD pathophysiology, insights into specific organ manifestations and the currently available treatments with the identification of potential therapeutic targets involved in AOSD pathogenesis will be outlined.

Occurrence and diversity of stem nodulation in Aeschynomene and Sesbania legumes from wetlands of Madagascar

Legumes have the ability to establish a nitrogen-fixing symbiosis with soil rhizobia that they house in specific organs, the nodules. In most rhizobium-legume interactions, nodulation occurs on the root. However, certain tropical legumes growing in wetlands possess a unique trait: the capacity to form rhizobia-harbouring nodules on the stem. Despite the originality of the stem nodulation process, its occurrence and diversity in waterlogging-tolerant legumes remains underexplored, impeding a comprehensive analysis of its genetics and biology. Here, we aimed at filling this gap by surveying stem nodulation in legume species-rich wetlands of Madagascar. Stem nodulation was readily observed in eight hydrophytic species of the legume genera, Aeschynomene and Sesbania, for which significant variations in stem nodule density and morphology was documented. Among these species, A. evenia, which is used as genetic model to study the rhizobial symbiosis, was found to be frequently stem-nodulated. Two other Aeschynomene species, A. cristata and A. uniflora, were evidenced to display a profuse stem-nodulation as occurs in S. rostrata. These findings extend our knowledge on legumes species that are endowed with stem nodulation and further indicate that A. evenia, A. cristata, A. uniflora and S. rostrata are of special interest for the study of stem nodulation. As such, these legume species represent opportunities to investigate different modalities of the nitrogen-fixing symbiosis and this knowledge could provide cues for the engineering of nitrogen-fixation in non-legume crops.

Effect of Feeding Level on Growth and Slaughter Performance, and Allometric Growth of Tissues and Organs in Female Growing Saanen Dairy Goats.

This study aimed to investigate the effect of feeding level on the growth and slaughter performance, and allometric growth of tissues and organs in female growing dairy goats. The trial included 10-20 and 20-30 kg weight stages with 48 female goat kids. The 24 goat kids in each stage were divided into 8 blocks based on weight, with 3 kids per block. Then, three kids from each block were randomly assigned to one of the three treatments, namely ad libitum (AL100), 70% of ad libitum (AL70), or 40% of ad libitum (AL40). The slaughter trial was conducted when the AL100 kids reached the target weight of 20 or 30 kg. The results showed that the ADG and feed conversion rate showed a linear decline as the feed level decreased (p < 0.05). Compared with the AL70 and AL100 groups, the AL40 group exhibited lower shrunk body weight, empty body weight, hot carcass weight, net meat rate, carcass meat rate, and visceral fat weight (p < 0.05) in both stages. Moreover, the AL40 group showed lower weights for skin and mohair, blood, rumen, small intestine, large intestine, mammary gland, and uterus than the AL70 and AL100 groups (p < 0.05) in both stages. However, feeding level did not affect organ indices in the two stages (p > 0.05). The bone, skin and mohair were isometric (b ≈ 1), but the muscle, visceral fat, and most internal organs were positive (b > 1) in both stages. In conclusion, feeding level affects the growth and development of dairy goats, which vary depending on the body weight stage and specific tissues and organs.

Biodistribution of radiolabeled alpha-amanitin in mice: An Investigation

Mushroom poisonings caused by Amanita phalloides are the leading cause of mushroom-related deaths worldwide. Alpha-Amanitin (α-AMA), a toxic substance present in these mushrooms, is responsible for the resulting hepatotoxicity and nephrotoxicity. The objective of our study was to determine the distribution of α-AMA in Balb/c mice by labeling with Iodine-131.Mice were injected with a toxic dose (1.4 mg/kg) of α-AMA labeled with Iodine-131. The mice were sacrificed at the 1st, 2nd, 4th, 8th, 24th, and 48th hours under anesthesia. The organs of the mice were removed, and their biodistribution was assessed in all experiments. The percent injected dose per gram (ID/g %) value for kidney, liver, lung, and heart tissues at 1st hour were 1.59 ± 0.07, 1.25 ± 0.33, 3.67 ± 0.80 and 1.07 ± 0.01 respectively.This study provides insights into the potential long-term effects of α-AMA accumulation in specific organs. Additionally, this study has generated essential data that can be used to demonstrate the impact of antidotes on the biological distribution of α-AMA in future toxicity models.

Gene co-expression network analysis in areca floral organ and the potential role of the AcMADS17 and AcMADS23 in transgenic Arabidopsis

Areca catechu L., a monocot belonging to the palm family, is monoecious, with female and male flowers separately distributed on the same inflorescence. To discover the molecular mechanism of flower development in Areca, we sequenced different floral samples to generate tissue-specific transcriptomic profiles. We conducted a comparative analysis of the transcriptomic profiles of apical sections of the inflorescence with male flowers and the basal section of the inflorescence with female flowers. Based on the RNA sequencing dataset, we applied weighted gene co-expression network analysis (WGCNA) to identify sepal, petal, stamen, stigma and other specific modules as well as hub genes involved in specific floral organ development. The syntenic and expression patterns of AcMADS-box genes were analyzed in detail. Furthermore, we analyzed the open chromatin regions and transcription factor PI binding sites in male and female flowers by assay for transposase-accessible chromatin sequencing (ATAC-seq) assay. Heterologous expression revealed the important role of AcMADS17 and AcMADS23 in floral organ development. Our results provide a valuable genomic resource for the functional analysis of floral organ development in Areca.

Serum Level of Immunosuppressants as a Marker of Effectiveness of Pharmaceutical Education in Solid Organ Transplantation

Solid organ transplantation promotes an increase in the quality of life of those with diseases that compromise the functioning of a specific organ, maximizing graft survival and reducing the need for retransplantation is essential. Post-transplant medication adherence is one of the factors that influence positive clinical outcomes, with this, the importance of pharmacotherapeutic follow-up at the hospital and outpatient level with the clinical pharmacist is addressed. Objectives: To verify the impact of pharmacotherapeutic guidance and follow-up on the compliance of serum levels of calcineurin inhibitors in lung and liver transplant patients. Methods: Descriptive and retrospective study with adult liver and lung transplant patients using calcineurin inhibitors, aged over 18 years, between 2018 and 2020. The variation index was calculated through the mean and standard deviation of serum levels collected during the index hospitalization, being used to assess the adequacy of serum levels in three different periods. Results: A total of 84 patients were transplanted, including 64 patients (45 liver transplants and 19 lung transplants). In a subgroup analysis, 42.22% of the liver patients and 47.37% of the lung transplant recipients did not have the same serum level in the first post-discharge consultation. After 1 year of transplantation and differentiated outpatient follow-ups, the target serum levels were reached in 63.16% and 77.78% of the studied populations, respectively. Conclusion: The importance of clinical action was demonstrated from the reflection obtained on the adequacy and conformity of serum levels of calcineurin inhibitors, not only at the hospital level but mainly on the pharmacotherapeutic follow-up carried out on an outpatient basis, in which we observed a more expressive value.

Semiquantitative 18F-FDG PET/CT in monitoring glucocorticoid response of immunoglobulin G4-related effusive constrictive pericarditis: a case report

BackgroundImmunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP.Case presentationHerein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient’s condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine.ConclusionThe rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.

Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.

A comparative study of secondary metabolites profiling and biological activity of Smyrnium olusatrum L. leaf, flower and fruit

Essential oil (EO) composition of Smyrnium olusatrum was characterised by high proportion of furanosesquiterpenes (51.66–69.35%). The leaf methanolic extract composition was found to be rich with Quercetin-O-hexoside (39.78%). Apigenin 6,8-di-Chexoside represent the major component of flower (18.2%) and fruits (18.82%). Flower extract exhibited the highest contents of total phenolic (48.97 mg GAE/g) and flavonoid (52.63 mg RE/g). The β-carotene and lycopene contents were in the order of 4.55-26.14 mg/100g, and 8.00-49.45 mg/100g, respectively. Methanolic extracts and EOs of different organs were found to possess antioxidant activities, as determined by scavenging effect, chelating activity and β-carotene-linoleic acid model system. Furthermore, Fruit S. olusatrum EO exhibited a potent inhibitory activity against Acetylcholinesterase, while the methanolic extract showed a weaker activity. The methanolic extract displayed inhibitory effects on α-amylase, whereas the EOs was not as efficient in inhibiting this enzyme. The observed level of biological activities varied depending on the specific extracts and organs studied.

Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

Prognostic significance of tumour budding in noncolorectal gastrointestinal tract and pancreatobiliary tract: a systematic review and meta-analysis.

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.

Regenerative Medicine and Nanotechnology approaches against Cardiovascular Diseases: Recent Advances and Future Prospective.

Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.

Organ/Cell-Selective Intracellular Delivery of Biologics via N-Acetylated Galactosamine-Functionalized Polydisulfide Conjugates.

Biologics, including proteins and antisense oligonucleotides (ASOs), face significant challenges when it comes to achieving intracellular delivery within specific organs or cells through systemic administrations. In this study, we present a novel approach for delivering proteins and ASOs to liver cells, both in vitro and in vivo, using conjugates that tether N-acetylated galactosamine (GalNAc)-functionalized, cell-penetrating polydisulfides (PDSs). The method involves the thiol-bearing cargo-mediated ring-opening polymerization of GalNAc-functionalized lipoamide monomers through the so-called aggregation-induced polymerization, leading to the formation of site-specific protein/ASO-PDS conjugates with narrow dispersity. The hepatocyte-selective intracellular delivery of the conjugates arises from a combination of factors, including first GalNAc binding with ASGPR receptors on liver cells, leading to cell immobilization, and the subsequent thiol-disulfide exchange occurring on the cell surface, promoting internalization. Our findings emphasize the critical role of the close proximity of the PDS backbone to the cell surface, as it governs the success of thiol-disulfide exchange and, consequently, cell penetration. These conjugates hold tremendous potential in overcoming the various biological barriers encountered during systemic and cell-specific delivery of biomacromolecular cargos, opening up new avenues for the diagnosis and treatment of a range of liver-targeting diseases.

Immune-Related Adverse Events of Immune Checkpoint Inhibitors.

Immune-related adverse events (irAEs) are toxicities that arise after the administration of monoclonal antibodies targeting immune checkpoints (immune checkpoint inhibitors [ICIs]) in patients with cancer. They can occur at any time after initiation of ICI treatment, with a broad clinical phenotype that can be organ-specific or systemic. Although most irAEs manifest as mild to moderate signs and symptoms, severe forms of irAEs can lead to irreversible organ failure and have acute life-threatening presentations. Treatment should be tailored to the specific organ involved and the severity. Glucocorticoids are the first-line treatment for most irAEs, with immunosuppressants and biologics mainly used as second-line treatments.