An updated patent review of GLP-1 receptor agonists (2020-present).

INTRODUCTION: Type 2 diabetes (T2DM) and obesity present significant global health issues, requiring the development of long-lasting and highly effective pharmacotherapies. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used for diabetes treatment, their potential for addressing obesity is still being explored. AREAS COVERED: This review offers a comprehensive overview of recently published patents from January 2020 to July 2023, focusing on modified GLP-1RAs, small molecule GLP-1RAs, GLP-1 R-based multi-agonists, GLP-1RA-based fusion proteins, and combination therapies. The patents discussed pertain to the treatment and prevention of diabetes and obesity. Patent searches were conducted using the PATENTSCOPE database of the World Intellectual Property Organization, using the keywords GLP-1, GLP-1/GIP, GLP-1/GCG, and GLP-1/GCG/GIP. EXPERT OPINION: In recent years, patents have emphasized two main goals for developing GLP-1RAs drugs: oral delivery and improved weight reduction effects. To address the growing demand for improved treatments, researchers have focused their efforts on developing GLP-1 R-based multi-agonists, orally administered GLP-1RAs, and combination therapies utilizing GLP-1RAs. These new approaches offer promising benefits, such as improved effectiveness by targeting multiple pathways and reduced side effects. Additionally, the development of new uses, oral forms, and long-lasting preparations will be crucial in shaping the future market potential of GLP-1 drugs.

Case report of a patient with Erdheim-Chester disease presenting with neuro-endocrine symptoms and negative for BRAF mutation.

RATIONALE: Erdheim-Chester disease (ECD) is a rare progressive disease affecting multiple systems. It has recently been recognized as a neoplastic disease following the discovery of activating mutations in the MAPK pathway. There are several striking signs of ECD, such as the long bone involvement, as well as the hairy kidney appearance on computed tomography scan. It is rare for ECD to manifest neurological symptoms. Central nervous system involvement is a strong prognostic factor and independent predictor of death. ECD is characterized by the overproduction and accumulation of foamy histiocytes and Touton's giant cells in various tissues and organs. ECD is a multisystem disorder in which any organ may be affected. PATIENT CONCERNS: This case report describes a 57-year-old woman with headaches and ataxia as the first clinical manifestation, without characteristic bone pain, but with delayed enuresis. In addition to the renal involvement, this patient had rarer splenic involvement. DIAGNOSES: The imaging presentation of this patient was similar to that of a "multiple meningiomas". A combination of clinical, imaging and pathology for the diagnosis of ECD. INTERVENTIONS: Patients were given INF-α therapy. OUTCOMES: Fortunately, the patient responded well to INF-α treatment. LESSONS: ECD patient with neuro-endocrine symptoms.

Lymphomatoid granulomatosis with the central nervous system involvement as the main manifestation: a case report.

BACKGROUND: Lymphomatoid granulomatosis (LyG) is a rare extralymphatic lymphoproliferative disease characterized by lymphocytic invasion into vascular walls and damage to blood vessels. The lungs are affected in 90% of LyG cases, followed by the skin, central nervous system (CNS), kidneys and liver. CASE PRESENTATION: Here we report a case of a young woman with LyG, with CNS involvement as the initial clinical manifestation. Computer tomography (CT) scans showed multiple nodular, patchy and flocculent high-density shadows in both lungs without mediastinal lymph node enlargement. Magnetic resonance imaging (MRI) scans showed multiple abnormal signal intensities in the right cerebellar hemisphere, frontal, parietal and temporal lobes, and dorsal brainstem, which became patchy and annular after enhancement. The post-operative pathological analysis of lesion samples confirmed the diagnosis of grade II LyG. CONCLUSIONS: LyG should be concerned in young adults showing multiple radiological brain and lung lesions. Resection and postoperative medication of steroid hormones and IFN-α may be effective in the treatment of LyG.

Characterization of the Mitochondrial Genome of a Wheat AL-Type Male Sterility Line and the Candidate CMS Gene.

Heterosis utilization is very important in hybrid seed production. An AL-type cytoplasmic male sterile (CMS) line has been used in wheat-hybrid seed production, but its sterility mechanism has not been explored. In the present study, we sequenced and verified the candidate CMS gene in the AL-type sterile line (AL18A) and its maintainer line (AL18B). In the late uni-nucleate stage, the tapetum cells of AL18A showed delayed programmed cell death (PCD) and termination of microspore at the bi-nucleate stage. As compared to AL18B, the AL18A line produced 100% aborted pollens. The mitochondrial genomes of AL18A and AL18B were sequenced using the next generation sequencing such as Hiseq and PacBio. It was found that the mitochondrial genome of AL18A had 99% similarity with that of Triticum timopheevii, AL18B was identical to that of Triticum aestivum cv. Chinese Yumai. Based on transmembrane structure prediction, 12 orfs were selected as candidate CMS genes, including a previously suggested orf256. Only the lines harboring orf279 showed sterility in the transgenic Arabidopsis system, indicating that orf279 is the CMS gene in the AL-type wheat CMS lines. These results provide a theoretical basis and data support to further analyze the mechanism of AL-type cytoplasmic male sterility in wheat.

A wheat dominant dwarfing line with Rht12, which reduces stem cell length and affects gibberellic acid synthesis, is a 5AL terminal deletion line.

Dwarfing and semi-dwarfing are important agronomic traits that have great potential for the improvement of wheat yields. Rht12, a dominant gibberellic acid (GA)-responsive dwarfing gene from the gamma-ray-induced wheat mutant Karcagi 522M7K, is located in the long arm of chromosome 5A, which is closely linked with the locus Xwmc410. Rht12 is likely an ideal gene for GA biosynthesis and deactivation research in common wheat. However, information on the Rht12 locus and sequence is lacking. In this study, Rht12 significantly shortened stem cell length and decreased GA biosynthetic components. Using bulked segregant RNA-Seq, wheat 660k single nucleotide polymorphism chip detection, and newly developed simple sequence repeat markers, Rht12 was mapped to a 11.21-Mb region at the terminal end of chromosome 5AL, and was found to be closely linked with the Xw5ac207SSR marker with a 10.73-Mb fragment deletion in all of the homologous dwarfing plants. Transcriptome analyses of the remaining 483-kb region showed significantly higher expression of the TraesCS5A01G543100 gene encoding the GA metabolic enzyme GA 2-ß-dioxygenase in dwarfing plants than in high stalk plants, suggesting that Rht12 reduces plant height by activating TaGA2ox-A14. Taken together, our findings will promote cloning and functional studies of Rht12 in common wheat.

Quantitative investigation of the poly-adenine DNA dissociation from the surface of gold nanoparticles.

In recent years, poly adenine (polyA) DNA functionalized gold nanoparticles (AuNPs) free of modifications was fabricated with high density of DNA attachment and high hybridization ability similar to those of its thiolated counterpart. This nanoconjugate utilized poly adenine as an anchoring block for binding with the AuNPs surface thereby facilitated the appended recognition block a better upright conformation for hybridization, demonstrating its great potential to be a tunable plasmonic biosensor. It's one of the key points for any of the practical applications to maintaining stable conjugation between DNA oligonucleotides and gold nanoparticles under various experimental treatments. Thus, in this research, we designed a simple but sensitive fluorescence turn-on strategy to systematically investigate and quantified the dissociation of polyA DNA on gold nanoparticles in diverse experimental conditions. DNA desorbed spontaneously as a function of elevated temperature, ion strength, buffer pH, organic solvents and keeping time. What's more, evaluating this conjugate stability as affected by the length of its polyA anchor was another crucial aspect in our study. With the improved understanding from these results, we were able to control some of our experimental conditions to maintain a good stability of this kind of polyA DNA-AuNPs nanoconjugates.