Neurodegenerative disorders, which include Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.

The immune checkpoint blockade therapy has completely transformed cancer treatment modalities because of its unprecedented and durable clinical responses in various cancers. With the increasing use of immune checkpoint blockades in clinical practice, a large number of patients develop acquired resistance. However, the knowledge about acquired resistance to immune checkpoint blockades is limited and poorly summarized. In this review, we clarify the principal elements of acquired resistance to immune checkpoint blockades. The definition of acquired resistance is heterogeneous among groups or societies, but the expert consensus of The Society for Immunotherapy of Cancer can be referred. Oligo-progression is the main pattern of acquired resistance. Acquired resistance can be derived from the selection of resistant cancer cell clones that exist in the tumor mass before therapeutic intervention or gradual acquisition in the sensitive cancer cells. Specifically, tumor intrinsic mechanisms include neoantigen depletion, defects in antigen presentation machinery, aberrations of interferon signaling, tumor-induced exclusion/immunosuppression, and tumor cell plasticity. Tumor extrinsic mechanisms include upregulation of other immune checkpoints. Presently, a set of treatment modalities is applied to patients with similar clinical characteristics or resistance mechanisms for overcoming acquired resistance, and hence, further research is required.

Hepatocellular carcinoma (HCC) is highly incidental in South Asian countries. Nepal, however, has low incidence for HCC owing to low prevalence for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Nepal lacked national cancer registry until 2003. Though there has been some effort in having one, the current registry incorporates twelve centers and may not properly represent the total cancer burden in the country. Serology for HBV and HCV is seen to be positive in nearly 25 to 30% and 5 to 10% of HCCs respectively. Clinical characteristics of HCCs in Nepal have been discussed in this mini-review and it features poor performance status and advanced stage at presentation, making only a small fraction of these subjects eligible for curative treatment options. Most of the standard treatment modalities are available in Nepal and appear to be reasonably affordable as compared with other developed nations. How to cite this article: Shrestha A. Liver Cancer in Nepal. Euroasian J Hepato-Gastroenterol 2018;8(1):63-65.

Cardiovascular Diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also underlying drug delivery obstacles that must be addressed. Challenges in drug delivery warrant further studies for the development of novel and more efficacious medical therapies. An extensive understanding of the molecular mechanisms of disease in combination with current challenges in drug delivery serves as a platform for the development of novel drug therapeutic targets for CVD. The objective of this article is to review the pathogenesis of atherosclerosis, first-line medical treatment for CVD, and key obstacles in an efficient drug delivery.

BACKGROUND: Rheumatoid Arthritis (RA) is an inflammatory disease with destructive pattern. Patients are suffering from pain and decreased functional outcome as the disease progress. Certain joints are widely discussed in the literature as well as shoulder girdle, but shoulder girdle surgical treatment options\' indications and superiorities to each other were not compared entirely.
METHODS: Treatment options, such as; synovectomy and bursectomy, resection interposition arthroplasty, hemiarthroplasty, humeral resurfacing arthroplasty, anatomical total shoulder arthroplasty and reverse shoulder arthroplasty, are examined for their timing, advantages, disadvantages and comparison.
RESULTS: Patients\' age is the main factor about the decision making in rheumatoid arthritis. Young aged patients demand high activity level, but as a result loosening of the implant is frequently encountered. Thus, the protection of the bone stock as much as possible must be the priority. For a young patient with disabling pain should be evaluated for less invasive surgeries such as; synovectomy and bursectomy, resection interposition arthroplasty and also for hemiarthroplasty for preservation of glenoid bone stock. But rotator cuff status, glenoid bone stock evaluation and grading of the glenoid defect become more important in old aged patients and the correct decision making can only be made by combining these factors.
CONCLUSIONS: Age, functional demand, rotator cuff status and adequacy of glenoid bone stock are defined as major criteria for an optimal treatment. Even though RA patients require additional care for a good functional outcome; with correct decision-making, high quality of life is achievable.