Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma.

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques. Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes.

The Roles of Serotonin in Neuropsychiatric Disorders.

The serotonergic system extends throughout the central nervous system (CNS) and the gastrointestinal (GI) tract. In the CNS, serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. These processes are mediated through 5-HT binding to 5-HT receptors (5-HTRs), are classified into seven distinct groups. Deficits in the serotonergic system can result in various pathological conditions, particularly depression, schizophrenia, mood disorders, and autism. In this review, we outlined the complexity of serotonergic modulation of physiologic and pathologic processes. Moreover, we provided experimental and clinical evidence of 5-HT's involvement in neuropsychiatric disorders and discussed the molecular mechanisms that underlie these illnesses and contribute to the new therapies.

Facilitators and barriers to self-management in Iranian men with chronic obstructive pulmonary disease: a qualitative study.

INTRODUCTION: Self-management, as the most common method of chronic obstructive pulmonary disease (COPD) management, is not an isolated behaviour, but a set of physical, social, cultural, psychological and existential factors affecting it. AIM: This study aimed to explore the facilitators and barriers to self-management in men with COPD in the unique social, cultural, political and economic context of Iran. METHODS: This paper reports part of the findings of a qualitative grounded theory study aimed at exploring the process of self-management in Iranian men with COPD, which was conducted in Iran from January 2019 to July 2023. Participants included men with COPD, their family members and pulmonologists. The selection of participants in this research began with the purposeful sampling method. Data was collected using semistructured interviews. Data collection continued until the data saturation was achieved. A total of 15 interviews were conducted with nine patients, three family members of patients and three pulmonologists. The data was analysed using the constant comparative analysis method. RESULTS: The findings of this study showed that knowledge, education, experience, family involvement and financial support are the factors that facilitate self-management. Factors related to deficits include lack of education, lack of treatment support, family cooperation deficit, financial problems, medication obtaining problems and factors related to disease impacts include specific nature of the disease, residual effect, comorbidity and factors related to negative patients characteristics include false beliefs, poor self-efficacy, feeling shame and non-adherence are barriers to self-management in men with COPD. CONCLUSION: Based on results of this study, healthcare providers and health planners can strengthen the factors that facilitate self-management and weaken or remove the barriers to self-management, so that these patients use self-management strategies with maximum capacity to control the disease.

Inorganic nanoparticle-cored dendrimers for biomedical applications: A review.

Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their distinctive structure and chemical/physical properties. Surface modifiers play a pivotal role in shaping INPs' primary attributes, influencing their physicochemical properties, stability, and functional applications. Among these modifiers, dendrimers have gained attention as highly effective multifunctional agents for INPs, owing to their unique structural qualities, dendritic effects, and physicochemical properties. Dendrimers can be seamlessly integrated with diverse inorganic nanostructures, including metal NPs, carbon nanostructures, silica NPs, and QDs. Two viable approaches to achieving this integration involve either growing or grafting dendrimers, resulting in inorganic nanostructure-cored dendrimers. The initial step involves functionalizing the nanostructures' surface, followed by the generation of dendrimers through stepwise growth or attachment of pre-synthesized dendrimer branches. This hybridization imparts superior qualities to the resulting structure, including biocompatibility, solubility, high cargo loading capacity, and substantial functionalization potential. Combining the unique properties of dendrimers with those of the inorganic nanostructure cores creates a multifunctional system suitable for diverse applications such as theranostics, bio-sensing, component isolation, chemotherapy, and cargo-carrying applications. This review summarizes the recent developments, with a specific focus on the last five years, within the realm of dendrimers. It delves into their role as modifiers of INPs and explores the potential applications of INP-cored dendrimers in the biomedical applications.

VU0155041, a positive allosteric modulator of mGluR4, in the nucleus accumbens facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats.

Nucleus accumbens (NAc) neurons appear to be at the hub of the reward circuit. New evidence suggests that the behavioural effects of morphine substances may be significantly regulated by glutamate-mediated transmission, notably by metabotropic glutamate (mGlu) receptors. Here, we examined the hypothesis that the mGlu4 receptor within that NAc has a role in the extinction and reinstatement of morphine-induced conditioned place preference (CPP). The animals received bilaterally microinjections of VU0155041, a positive allosteric modulator (PAM) and partial agonist of mGlu4 receptor, into the NAc. In Experiment 1, the rats received VU0155041 (10, 30 and 50 µg/0.5 µL) during the extinction period. In Experiment 2, the CPP extinguished rats received VU0155041 (10, 30 and 50 µg/0.5 µL) five minutes prior to the administration of morphine (1 mg/kg) in order to reinstate the extinguished CPP. The results showed that the intra-accumbal administration of VU0155041 reduced the extinction period of CPP. Furthermore, the administration of VU0155041 into the NAc dose-dependently inhibited the reinstatement of CPP. The findings suggested that the mGluR4 in the NAc facilitates the extinction and inhibits the reinstatement of the morphine-induced CPP, which could be mediated by an increase in the release of extracellular glutamate.

Association of MGLL Intronic C>T Single Nucleotide Polymorphism (rs782440) with Borderline Personality Disorder: A Case-Control Study.

OBJECTIVE: From the perspective of etiology, borderline personality disorder (BPD) is a multifactorial and complex disorder, hence our understanding about the molecular basis and signaling of this disorder is extremely limited. The purpose of this study was evaluating the relationship between BPD and the Monoacylglycerol lipase (MGLL) polymorphism rs782440 in the population of Hamadan, Iran. MATERIALS AND METHODS: In this case-control study, 106 participants including 53 patients with BPD and 53 healthy control subjects were selected by psychiatrists in the Department of Psychiatry at Farshchian Sina Hospital in Hamadan. The BPD patients were selected based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) form for diagnosing BPD patients. For genotyping, polymerase chain reaction (PCR) was used to amplify the desired region including the (MGLL) intronic C>T single nucleotide polymorphism (SNP) (rs782440) and afterward the amplicon was sequenced using the Sanger sequencing method. To determine the genotype of these patients, their sequences were aligned with the reference sequence of MGLL through the CLC genomic workbench software. RESULTS: The results indicated that the frequency of TT in comparison to the CC genotype was significantly different (P=0.003) and the risk of BPD in change from the TT genotype to CC genotype was increased by 6.679%. Regarding the frequency of allele in this group, no significant difference was observed. CONCLUSION: This paper, has studied and reports for the first time, the association between MGLL SNP (rs782440) with BPD. The findings of the current research revealed that the TT genotype increases the risk of BPD compared to the CC genotype. Considering the lack of a suitable diagnostic biomarker for BPD, using this potential biomarker in the near future can be promising.

Extreme capsule is a bottleneck for ventral pathway.

As neuroscience literature suggests, extreme capsule is considered a whiter matter tract. Nevertheless, it is not clear whether extreme capsule itself is an association fiber pathway or only a bottleneck for other association fibers to pass. Via our review, investigating anatomical position, connectivity and cognitive role of the bundles in extreme capsule, and by analyzing data from the dissection, it can be argued that extreme capsule is probably a bottleneck for the passage of uncinated fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF), and these fasciculi are responsible for the respective roles in language processing.