Medical Bulletin 19/ December/ 2024 - Video

The World Health Organization has called on Member countries in South-East Asia Region to build on the momentum created to end TB with accelerated multi-sectoral efforts led by the highest political level to reach every affected and at risk person, and address the socio-economic determinants and impact of the disease.

“A primary health care-based approach that addresses TB determinants such as undernutrition, embraces new technologies including developments in the field of Artificial Intelligence, and has communities and affected populations at the center of all efforts, should be among the key elements of our reinvigorated approach,” said Saima Wazed, Regional Director, WHO South-East Asia Region.

According to the Global TB Report 2024 published by the WHO, more than 3.8 million people were initiated on TB treatment in the WHO South-East Asia Region in 2023, the highest ever and nearly 1.3 million more than in the year 2020 impacted by the COVID-19 pandemic. The estimated percentage of people with TB, missed by the programme, declined to 22% from 44% in 2020.

As per the report, the estimated number of deaths due to TB declined to 583 000 in 2023, after a peak of 763 000 in 2021. However, the Region continues to account for a disproportionate 45% of the global TB burden with an estimated over 5 million people developing the disease in 2023, and over half of TB deaths globally in 2023.

Nearly 1.5 million people received TB preventive treatment which helps protect high-risk population from developing the disease. However, the coverage remained low with only 9% people living with HIV and less than a quarter for household contacts of bacteriologically confirmed TB patients, receiving preventive treatment.

Though countries in the Region have been making considerable efforts, the huge disease burden, its catastrophic socio-economic impact and severe resource crunch calls for accelerated and urgent actions, she said. There is need for multisectoral, multidisciplinary collaboration and coordination for pooling of resources to end TB, leaving no-one behind to reach every TB affected person, their families and those at risk of developing the disease irrespective of where they live. Reaching the unreached, specifically those who are vulnerable and marginalized is key to our fight against TB, the Regional Director said.

“It is time to push the pedal on the momentum built collectively by the Member countries of the Region in efforts towards ending TB,” Wazed said.

Reference: https://www.who.int/southeastasia/news/detail/16-12-2024-bolster-efforts-to-end-tb-in-who-south-east-asia-region

In a study published in the issue of Nature, a team of researchers discovered a new population of neurons that is responsive to the hormone leptin.

"We've long known that the hypothalamus, located deep in the brain, plays a role in hunger, hormone levels, stress responses, and body temperature," said Brian Herb, PhD, a scientist at IGS and a Research Associate of Pharmacology, Physiology, and Drug Development at UMSOM.

"Since our earlier research showed that unique regulatory programs in genes give rise to specialized neuronal populations -- it makes sense that this new research discovered a previously unknown set of neurons that regulate energy and food intake," Dr. Herb added

Through several experiments with mice, the researchers found that this previously unknown neuronal population that express both receptors for leptin and the BNC2 gene not only helps suppress hunger, but also responds to food-related sensory cues, such as food palatability and nutritional status.

Those mice ate more and gained more weight than control mice.

In addition, researchers added fluorescence to the BNC2 neurons and noticed when they fed mice after fasting, the BCN2 neurons activated, whereas previously known neuronal populations in the hypothalamus did not react.

BNC2 neurons in the hypothalamus, which are activated by the hunger hormone leptin, provide the potential for a completely new class of obesity drugs," said Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. "These drugs would be distinct from Ozempic and other GLP-1 agonists, which stimulate insulin secretion. Leptin-targeting drugs could be beneficial for those who can't tolerate GLP-agonists due to gastrointestinal side effects like nausea and stomach upset."

Reference: https://www.medschool.umaryland.edu/news/2024/researchers-discover-new-neurons-that-suppress-food-intake.html

In a recent study published in the journal Inorganic Chemistry, a team of researchers explored the potential of azolato-bridged dinuclear platinum(II) complexes (azolato-bridged complexes) in treating prostate cancer. The study particularly focused on a complex called 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2) as an alternative to cisplatin. These complexes are characterized by their water solubility and promising antiproliferative effects against prostate cancer cell lines, with minimal toxicity compared to traditional platinum-based drugs.

The team used a variety of methods to evaluate androgen receptor dynamics and therapeutic effects in LNCaP prostate cancer cells. They utilized azolato-bridged complexes, cisplatin, and the androgen receptor antagonist KW-365 to explore their efficacy and performed cell viability, gene expression, and protein analyses. Additionally, the team employed immunofluorescence staining to visualize AR expression and evaluated apoptosis (programmed cell death), cell cycle distribution, and nuclear platinum accumulation.

The results showed that 5-H-Y exhibited significantly stronger cytotoxic effects than cisplatin, with a low half-maximal inhibitory concentration for dihydrotestosterone (DHT)-induced cell proliferation. Moreover, 5-H-Y effectively suppressed the expression of androgen receptor-responsive genes. Immunofluorescence analysis confirmed that 5-H-Y promoted chromatin fragmentation, a hallmark of apoptosis, with greater efficacy observed at higher concentrations.

Despite its high antiproliferative activity, however, 5-H-Y demonstrated lower acute toxicity in vivo compared to other platinum complexes, making it a promising candidate for further development. “The azolato-bridged complexes used in this research are expected to play a key role in developing new treatments for advanced prostate cancer. For patients whose cancer has become resistant to conventional therapies, these complexes have the potential to effectively inhibit cancer progression with multi-layered attack while minimizing side effects. Our approach could thus expand treatment options for prostate cancer and improve the patient’s quality of life” says Associate Professor Yoshihisa Hirota from Shibaura Institute of Technology (SIT)

Reference: Arai, T., Oshima, M., Uemura, M., Matsunaga, T., Ashizawa, T., Suhara, Y., ... & Hirota, Y. (2024). Azolato-Bridged Dinuclear Platinum (II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity. Inorganic Chemistry, 63(44), 20951-20963.

Researchers from the National University of Singapore (NUS), in collaboration with Peking University, China, have made a discovery regarding the TRPV1 (transient receptor potential vanilloid 1) ion channel and its role in pain perception. The study reveals how solvent molecules can modulate pain signals, offering a potential pathway for a safer, non-addictive pain management approach.

The TRPV1 ion channel, essential for pain sensing, undergoes pore expansion when activated, allowing ions and larger molecules to pass through.

The research team led by Professor LIU Xiaogang from the Department of Chemistry at NUS developed an upconversion nanoprobe capable of distinguishing between ordinary water (H₂O) and deuterated water (D₂O). This advanced technology enabled real-time tracking of water dynamics at both the single-cell and single-molecule levels.

The study showed that when D₂O passed through the TRPV1 channel, it suppressed pain signal transmission and achieved effective analgesia.

The findings were published in the journal Nature Biomedical Engineering.

Administering D₂O to pre-clinical models, the team successfully reduced both acute and chronic inflammatory pain transmission without affecting other neurological responses.

This solvent-mediated analgesia mechanism provides an effective, biocompatible, and non-addictive alternative to traditional pain medications, circumventing issues related to drug dependency and tolerance.

Reference: Y Liu; Y He; J Tong; S Guo; X Zhang; Z Luo; L Sun; C Chang*; B Zhuang*; X Liu*, “Solvent-mediated analgesia via the suppression of water permeation through TRPV1 ion channels” Nature Biomedical Engineering DOI: 10.1038/s41551-024-01288-2 Published: 2024.