Maples Scientific Publisher brings together the best original research, analyses, reviews, news updates, practice updates, and thought-provoking editorials.
Category: biotech/medical – Page 1,268
Site-specific encoding of photoactivity and photoreactivity into antibody fragments
New light activated cancer treatment.
Several antibodies and antibody fragments have been previously developed for the treatment of various diseases, including cancer3,4. These antibodies bind to cell surface receptors expressed at higher levels on cancer cells, addressing a major challenge of selective cell targeting in cancer therapy. Although full-length antibodies have shown promise for treatment of several cancers, limited success has been demonstrated in eliminating solid tumors. Due to their large size, full-length antibodies are unable to diffuse deep into solid tumors5. In addition, it has been shown that high-affinity antibodies bind to the periphery of the tumor tissues, forming a barrier and preventing their further penetration6. Some studies in patients with cancer estimate that only 0.01% of the injected antibodies accumulate per gram of solid tumor tissue7. Small antibody fragments with low molecular weight can diffuse much deeper into tissues, presenting an excellent alternative to full-length antibodies. However, small antibody fragments have a low residence time in the body and often have a higher rate of dissociation (koff) from the target compared with full-length antibodies, limiting their clinical utility8. To address these challenges, antibody fragments are often multimerized9,10 and/or conjugated to larger proteins11, which increases the size of antibody fragments, again reducing their ability to penetrate into the tumor.
One solution to overcome the limitation of low residence time would be to replace the noncovalent interactions between the antibody fragment and its antigen with a covalent bond. In a notable effort, an affibody containing a photocrosslinker in its antigen binding region was shown to covalently link to its antigen and demonstrated higher accumulation on tumor tissues12. Another pioneering study involved developing affibodies containing a latent bioreactive amino acid in their antigen binding region that forms a covalent bond with the target antigen by proximity-dependent reaction without any external impetus13. However, the former had substantially lower binding affinity compared with its wild-type (wt) counterpart and thus, requires using a high concentration for efficient initial binding, while the latter could react with target antigen expressed on healthy cells causing side effects.
Although antibody-based therapeutics are more selective than several cytotoxic small molecule drugs used for cancer treatment, they can cause cardiac toxicity and skin reactions14. These side effects are due to the binding of the antibody to its receptor antigen expressed on healthy cells. This challenge could be addressed by activating antibody–antigen binding in the tumor microenvironment. One notable example in this direction is the development of antibodies containing an inhibitory N-terminal domain that is removed by tumor-specific proteases15. However, this approach would be difficult to extend to antibody fragments whose N terminus is not involved in antigen binding. We and others have also developed light-activated antibody fragments either by site-specific installation of photocaged functional groups or by introducing light-responsive proteins into antibodies16,17,18. In principle, such antibodies could be activated at the site of tumors using surgically implanted biocompatible light-emitting diodes (LEDs)19, thereby reducing the side effects of antibody-based therapeutics.
New tumor-selective light treatment could kill breast cancer cells with greater accuracy and improve tumor control
This is a nontoxic version of cancer treatment that works on any type of cancer.
Breast cancer is the most common cancer affecting women in Singapore. Treatment is multimodal and often involves surgery to remove the cancer and lymph nodes involved.
Adjuvant therapy, given after the initial treatment, is used to irradiate and destroy micrometastases, which are cancer cells in the blood stream or lymphatics, to decrease recurrence. This form of therapy is subdivided into local (radiotherapy) and systemic therapy (endocrine therapy, chemotherapy and targeted therapy).
Studies have shown that patient satisfaction has increased with breast conserving therapy (BCT) where only the tumor and a margin is removed from the body post mastectomy, compared to full mastectomy alone, which removes all parts of the breast. For BCT, radiotherapy has to be administered after lumpectomy, which removes other abnormal tissue from the breast and some normal tissue around it.
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‘Hallucinate’ chosen as Cambridge dictionary’s word of the year
The original definition of the chosen word is to “seem to see, hear, feel, or smell” something that does not exist, usually because of “a health condition or because you have taken a drug”
The psychological verb gained an extra meaning in 2023 that ‘gets to the heart of why people are talking about artificial intelligence’
Proteins Predict Signs of Alzheimer’s Disease
Protein indicators of subclinical peripheral heath in plasma were linked with markers of Alzheimer’s disease and neurodegeneration, cross-sectional proteomic analyses showed.
Greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with plasma biomarkers of amyloid-beta, phosphorylated tau181 (p-tau181), neurofilament light (NfL, a measure of neuronal injury), and glial fibrillary acidic protein (GFAP, a measure of astrogliosis), even in people without cardiovascular or kidney disease, reported Keenan Walker, PhD, of the National Institute on Aging in Baltimore, and co-authors.
Proteomic indicators of body fat percentage, lean body mass, and visceral fat also were tied to p-tau181, NfL, and GFAP, Walker and colleagues wrote in the Annals of Neurology.
You Are When You Eat
The sleep-wake cycle is among the most well-known circadian rhythms in the body and is severely affected in Alzheimer’s disease (AD). “Eighty percent of patients with AD suffer dysregulation or disruption of circadian rhythms, and the obvious clinical manifestations are the sleep-wake reversals,” Desplats said. “These patients are very sleepy during the day, agitated during the night, more confused, and sometimes aggressive.”
The feeding-fasting cycle is one of the strongest signals you can send the body to entrain the circadian clock.-Paula Desplats, University of California, San Diego
In a recent study published in Cell Metabolism, Desplats’s team used mice that are genetically engineered to develop AD to test whether intermittent fasting improves circadian rhythm abnormalities.3 Rather than restricting calories or making dietary changes, they simply limited food access to a defined six-hour daily window. They found that time-restricted eating improved sleep, metabolism, memory, and cognition, and reduced brain amyloid deposits and neuroinflammatory gene expression. “Many of the genes that are affected in AD are rhythmically expressed in the brain, meaning that they are in direct relation with the circadian clock and are involved in functions that are fundamental to AD pathology,” Desplats said. Intermittent fasting restored the rhythmic activity of these genes, but the real surprise was the extent to which it mitigated brain amyloid deposits and improved cognition and sleep-wake behaviors. “I didn’t expect that it will have such a dramatic impact on pathology,” Desplats said.
Biologists Unveil the First Living Yeast Cells With Over 50% Synthetic DNA
To get several of the modified chromosomes into the same yeast cell, Boeke’s team ran a lengthy cross-breeding program, mating cells with different combinations of genomes. At each step there was an extensive “debugging” process, as synthetic chromosomes interacted in unpredictable ways.
Using this approach, the team incorporated six full chromosomes and part of another one into a cell that survived and grew. They then developed a method called chromosome substitution to transfer the largest yeast chromosome from a donor cell, bumping the total to seven and a half and increasing the total amount of synthetic DNA to over 50 percent.
Getting all 17 synthetic chromosomes into a single cell will require considerable extra work, but crossing the halfway point is a significant achievement. And if the team can create yeast with a fully synthetic genome, it will mark a step change in our ability to manipulate the code of life.
New research maps 14 potential evolutionary dead ends for humanity and ways to avoid them
Humankind on the verge of evolutionary traps, a new study: …For the first time, scientists have used the concept of evolutionary traps on human societies at large.
For the first time, scientists have used the concept of evolutionary traps on human societies at large. They find that humankind risks getting stuck in 14 evolutionary dead ends, ranging from global climate tipping points to misaligned artificial intelligence, chemical pollution, and accelerating infectious diseases.
The evolution of humankind has been an extraordinary success story. But the Anthropocene—the proposed geological epoch shaped by us humans—is showing more and more cracks. Multiple global crises, such as the COVID-19 pandemic, climate change, food insecurity, financial crises, and conflicts have started to occur simultaneously in something which scientists refer to as a polycrisis.
Humans are incredibly creative as a species. We are able to innovate and adapt to many circumstances and can cooperate on surprisingly large scales. But these capabilities turn out to have unintentional consequences. Simply speaking, you could say that the human species has been too successful and, in some ways, too smart for its own future good, says Peter Søgaard Jørgensen, researcher at the Stockholm Resilience Center at Stockholm University and at the Royal Swedish Academy of Sciences’ Global Economic Dynamics and the Biosphere program and Anthropocene laboratory.