Danger Dust - What Else?

A senolytics trial in human idiopathic pulmonary fibrosis patients selectively ablating senescent cells using Dasatinib and Quercetin (DQ) alleviates physical dysfunction and circulating SASP factors which have been confirmed in a cohort of inflammatory disease.

Our data provide a rationale for trials of such anti-ageing drugs in patients with arthralgia at risk of developing RA which can be validated in future preclinical and clinical studies to explore dosing and treatment duration to delineate the therapeutic window and maximise therapeutic benefits of proposed geroprotective drugs.

Immunotherapy has revolutionized the treatment of various solid tumors by harnessing the body’s immune system to recognize and destroy cancer cells. However, its role in mesothelioma remains understudied and controversial. Prior large-scale trials incorporating surgery with systemic therapies failed to demonstrate consistent survival benefits, casting doubt on the utility of surgical resection. This study challenges that paradigm by incorporating immune checkpoint blockade in a strategic perioperative timeline, attempting to augment antitumor immunity when tumor burden is minimized.

One of the study’s most innovative features lies in its use of circulating tumor DNA (ctDNA) profiling. ctDNA refers to fragments of tumor-derived genetic material released into the bloodstream, offering a minimally invasive biomarker for real-time disease monitoring. Mesothelioma’s low mutational burden complicates traditional ctDNA detection, but the researchers applied an ultra-sensitive genome-wide sequencing approach. This technique enabled the detection of microscopic residual disease that imaging alone could not reveal, providing unprecedented insight into tumor dynamics at a molecular level.

Source:

Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses

https://www.nature.com/articles/s41591-025-03958-3#Sec1

Systemic lupus erythematosus (shortened to SLE) is a long-term autoimmune condition that affects many parts of the body, including the skin, joints, and internal organs. People living with SLE may experience different symptoms that can negatively affect quality of life. Only a few medicines that help control SLE symptoms are available, but they can result in unwanted side effects and may not improve all symptoms.

Two studies, POETYK SLE-1 and POETYK SLE-2, are currently testing the drug deucravacitinib, which is a pill taken by mouth. Deucravacitinib works differently than other available medicines by targeting a specific protein that plays an essential role in the body’s immune response; this could provide symptom relief, with fewer side effects. Deucravacitinib has been tested and approved for use in adults with psoriasis. Deucravacitinib has also been tested in adults with psoriatic arthritis with positive outcomes, and a study in a smaller group of adults with SLE has also shown benefits.

This paper describes the way deucravacitinib is being tested in POETYK SLE-1 and POETYK SLE-2, which will include a larger number of adults with SLE. These studies will take place all over the world, and individual participation in the main period of the study will last 1 year.

The participants in these studies will have the option to continue the study for 2 more years, for a total of about 3 years. Results will help doctors and scientists understand if deucravacitinib can improve symptoms in adults with SLE in a safe and effective way.

Air pollution was recently found to be associated with increased risk of developing dementia. Zhang et al. investigated the relationship between PM2.5, an index of particle pollution, and the development of Lewy body dementia (LBD), the second most common form of dementia. Epidemiological data showed that PM2.5 exposure was associated with an increased risk of developing LBD. In mice, nasal administration of PM2.5 led to brain atrophy due to the accumulation of pathological α-synuclein, loss of dopaminergic neurons in the substantia nigra, and impaired cognition and motor function. The results identify a potential mechanistic link between air pollution and the development of dementia.

Recent research has shed light on the enigmatic relationship between viral infections and autoimmune disorders, with a groundbreaking study exploring this connection in the context of Sjögren’s disease (SjD). Sjögren’s disease is a chronic autoimmune condition characterized primarily by lymphocytic infiltration of exocrine glands, leading to dry mouth and dry eyes, but its precise etiological drivers remain elusive. The study, conducted by Zhang et al., elucidates a novel virome signature in the saliva of patients with SjD and uncovers a compelling mechanistic link implicating a viral agent in triggering pathogenic autoimmunity.

In conclusion, Zhang and colleagues’ work delineates a compelling viral connection in Sjögren’s disease pathogenesis, highlighting Vientovirus capsid protein’s molecular mimicry of SSA/Ro52 autoantigens as a key driver of autoimmunity. Their comprehensive approach substantiates the viral trigger hypothesis, offering new vistas in understanding, diagnosing, and treating this enigmatic autoimmune syndrome.

Oct 2014

Crystalline silica is among the environmental exposures associated with increased risk of autoimmune diseases, including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. Silica exposure has also been related to the development of ANCA-associated vasculitides (AAV), but past studies appear to conflict as to the presence and magnitude of the associated risks of disease. We aimed to conduct a systematic review of the existing studies and meta-analysis of their results.

Conclusion

Despite moderate heterogeneity among studies, the totality of the evidence after meta-analysis points to an association between silica exposure and risk for developing AAV.

After discussion between nephrology, rheumatology, infectious disease, and pulmonology, he was admitted for expedited kidney biopsy and bronchoscopy.

Kidney biopsy revealed glomerulonephritis with 30% active crescents and both IgG and C3 deposition, not entirely typical for lupus or ANCA vasculitis but concerning for druginduced or infection-associated ANCA.

Bronchoscopy showed hemosiderin ladenmacrophages but BAL was inconsistent with diffuse alveolar hemorrhage and negative for tuberculosis through AFB stain and culture.

Since his quantiferon was positive and he had immigrated from a TB-endemic region, concern for miliary tuberculosis was high, so he underwent VATS lung biopsy which was consistent with silicosis based on pathology demonstrating nodular aggregates of dust-laden macrophages, fibrosis, and birefringent particles. A diagnosis of ANCA vasculitis associated with silicosis was made.

No Change

The Council received an enquiry from an MP on behalf of a constituent concerning a possible relationship between exposure to silica and asbestos and development of anti-neutrophil cytoplasmic antibodies (ANCA)- associated vasculitis. Reviews of the available scientific literature for these issues are given in this report.

28. Given the current evidence, IIAC does not consider that ANCA-associated vasculitis associated with silica exposure meets the criteria for prescription under the Industrial Injuries Scheme.

29.There is much less evidence relating asbestos exposures to ANCA-associated vasculitis and that also is not sufficient to meet the criteria for prescription under the Industrial Injuries Scheme.

A single dose of LSD eased anxiety symptoms for many folks and the benefits lasted up to three months, a new study reports.

By 12 weeks, the effects were still strong: 65% of patients taking the most effective dose (100 milligrams) continued to see improvements, and nearly half were considered to be in remission, according to the study.

Inside almost every human cell is DNA, a comprehensive instruction manual for building and maintaining the body. Genes in that manual contain the instructions for making proteins. But those instructions must travel from the cell's nucleus, where the DNA lives, to the outer region of the cell—the cytoplasm—where proteins are actually made.

That's where mRNA comes in. Like a messenger, it copies the instructions from the DNA in the nucleus and carries them out to the protein-making machinery. More mRNA typically means more protein—unless the mRNA is unstable and breaks down too quickly.

The team also found that several of the genetic variants linked to unstable mRNA had already been associated with autoimmune diseases in large-scale genetic studies.

"One insight from this project is that some disease-associated variants may be acting through effects on mRNA stability," said Xiao.

Using additional modeling, the researchers linked expression levels of these stability-regulated genes to diseases including allergic rhinitis, lupus, diabetes mellitus and multiple sclerosis. The findings suggest that mRNA stability—long overlooked—may be a key mechanism behind many immune-related diseases.

The popularity of breathwork as a therapeutic tool for psychological distress is rapidly expanding. Breathwork practices that increase ventilatory rate or depth, facilitated by music, can evoke subjective experiential states analogous to altered states of consciousness (ASCs) evoked by psychedelic substances. These states include components such as euphoria, bliss, and perceptual differences. However, the neurobiological mechanisms underlying the profound subjective effects of high ventilation breathwork (HVB) remain largely unknown and unexplored.

Conclusion

In conclusion, our exploratory experiments suggest that circuitries supporting the integration of interoceptive representations and processing of affective memories are putative neurobiological substrates of HVB-induced ASCs. Our findings indicate directions for future research towards a better understanding of HVB and ultimately harnessing such practices for future therapeutic applications.

The biological role of urate (uric acid) during primate evolution has been unclear ever since it was discovered over 100 years ago that humans have unusually high levels of the small molecule compared to most other mammals. Humans (including all apes) are uncharacteristically susceptible to the build-up of urate because we no longer have a functional uricase enzyme capable of oxidizing this highly insoluble molecule.

We have now utilized CRISPR technology to insert functional ancestral uricase into the genome of human liver cells to address recent metabolic hypotheses that our ancestral primates inactivated uricase as a mechanism to increase triglyceride production in response to fructose and/or starvation. Uricase expression is confirmed in both hepatocyte monolayer and spheroid tissue cultures, and its expression reduces intracellular urate levels. The presence of uricase is also shown to prevent an increase in triglyceride production upon cellular uptake of fructose in both culture conditions.

Our results make progress that further describes a potential advantageous biological role of urate during primate evolution.

From carbonated water to carbonated rock

While most carbon projects focus on offshore storage, CarbFix2's terrestrial approach marks a vital shift: it speeds up natural mineralization processes within basalt, a volcanic rock formed from cooling lava.

At Hellisheiði, CO2 is captured from the geothermal plant and two direct air capture units. The CO2 gas is dissolved in water—much like making a fizzy drink—and pumped deep into porous layers of basalt, where minerals in the rock react with the CO2 and turn it into solid carbonate rock.

Cancer cells have one relentless goal: to grow and divide. While most stick together within the original tumor, some rogue cells break away to traverse to distant organs. There, they can lie dormant—undetectable and not dividing—for years, like landmines waiting to go off......

This awakening of dormant cancer cells, they've discovered, isn't a spontaneous process. Instead, the wake-up call comes from the inflamed tissue surrounding the cells. One trigger for this inflammation is bleomycin, a common chemotherapy drug that can scar and thicken lung tissue.

"The inflammation jolts the dormant cancer cells awake," Weinberg says. "Once awakened, they start multiplying again, seeding new life-threatening tumors in the body."

A protein particle hidden within the SARS-CoV-2 virus could lead to longer-lasting, more protective vaccines for COVID-19.

Scientists from La Trobe University and Kumamoto University in Japan have discovered that the body's immune system strongly reacts to an internal protein from SARS-CoV-2, the virus that causes COVID-19, which mutates less frequently than the surface-spike protein currently targeted by vaccines.

Source:

Molecular basis of potent antiviral HLA-C-restricted CD8+ T cell response to an immunodominant SARS-CoV-2 nucleocapsid epitope

https://www.nature.com/articles/s41467-025-63288-3

TB detection has made significant advances in recent years, including using artificial intelligence tools in conjunction with lung scans. However, many areas that are burdened most by TB, such as rural villages or low-income urban communities, do not have access to these tools.

While the use of molecular detection devices, such as one called GeneXpert, have become more widespread, a clinic may only have one of these devices and it can take two hours to process a sample. Overburdened clinics turn to the centuries-old technique of microscopy, or investigation of sputum under a microscope, which is both fallible and time-consuming.

"Human error may result in a person being told they are disease-free when they are not," said Stanesloaus. "Using rats is a very effective initiative."

APOPO's rats can scan 100 samples in 20 minutes, and since the program's inception, the rats have been able to identify more than 30,000 patients who had been sent home with a clean bill of health but were actually carrying TB, said Cox. The NGO is able to do with one lab what 55 hospitals do in a day, he adds.

Yet using live animals in the place of medical devices poses challenges, especially when it comes to scale. Samples have to be brought directly to a lab with enough trained rats to conduct the detection, with some samples brought to Morogoro by motorbike each day. Operations are most effective in dense urban centers.

The Central Pollution Control Board (CPCB), acting on directives from the Prime Minister’s Office (PMO), has instructed the Member Secretary of the West Bengal Pollution Control Board (WBPCB) to submit a report on the rising cases of silicosis in the industrial belt of Asansol under West Burdwan district.

Reports indicate there has been no regular health check-up of workers employed in silica manufacturing units in Salanpur Block, while pollution levels continue to worsen.

Hundreds of residents of Barabhui village in Salanpur are reported to be suffering from silicosis. Following intervention by the National Human Rights Commission (NHRC), the Chief Medical Officer of Health (CMOH) of West Burdwan sent a medical team to the village and set up a medical board to identify patients at Asansol District Hospital.

The NHRC had acted on a complaint filed by activist Amarnath Mahato and directed district magistrate S Ponnambalam to investigate the matter and submit reports to New Delhi. An ADM was sent to the site, followed by a series of review meetings.

Meanwhile, two more silicosis patients have died. So far, at least four to five people in Salanpur have lost their lives to the disease. One victim, misdiagnosed earlier, was later correctly identified at a private super-speciality hospital in Chennai and treated in Durgapur before succumbing.

In a distant galaxy called Makani, particles of dust were warmed by the light of newborn stars before being flung out into space by a massive starburst-driven wind. Over the course of 100 million years, the dust traveled farther and farther from Makani's center, ultimately ending up in the reservoir of hot gas that surrounds a galaxy, known as the circumgalactic medium (CGM).

Participants who used smartphones on the toilet were younger than non-users (mean ages 55.4 vs. 62.1, p = 0.001). Of all respondents, 66% used smartphones while on the toilet.

Participants who used smartphones on the toilet spent significantly more time there than those who did not, with 37.3% of smartphone users spending more than five minutes per visit on the toilet, compared to 7.1% of non-smartphone users (p = 0.006).

Furthermore, in a multivariate logistic regression, smartphone use on the toilet was associated with a 46% increased risk of hemorrhoids (p = 0.044) after adjusting for age, sex, BMI, exercise activity, straining and fiber intake.

The most common activity performed while on the toilet was reading “news” (54.3%), followed by “social media” (44.4%).

The study suggests that prolonged engagement with smartphones while using the toilet may be associated with an increased prevalence of hemorrhoids.

Billions upon billions of soot particles enter Earth's atmosphere each second, totaling about 5.8 million metric tons a year—posing a climate-warming impact previously estimated at almost one-third that of carbon dioxide.

Now, researchers say the climate-altering properties of these particles can change within just hours of becoming airborne, rather than days as previously assumed.

"Until now, models treated soot particles as simple spheres, but in reality, soot particles are aggregates—clumps of many smaller particles. The lace-like shape lets soot collect chemicals much faster than previously thought," Khalizov explained. "That means soot's climate properties evolve quicker, affecting both its warming and cooling effects, and also its lifetime."

Researchers led by Freedman et al. have made significant strides in understanding the complex mechanisms underlying diffuse systemic sclerosis, a challenging autoimmune disorder characterized by widespread fibrosis and vascular abnormalities. In their recent study, published in “Military Medical Research,” the team’s focus on extracellular BAG3 offers promising new insights that could reshape how we approach diagnosis and treatment for this debilitating condition. The elevation of BAG3 levels in early diffuse systemic sclerosis provides a potential biomarker for early detection, shedding light on the intricate biological pathways that contribute to disease progression.

Systemic sclerosis, commonly referred to as scleroderma, presents a unique array of clinical manifestations, often starting insidiously and progressing unpredictably. This highlights the need for effective biomarkers that can signal the onset and enable earlier therapeutic interventions. Freedman and colleagues have identified that BAG3, a member of the Bcl-2-associated athanogene protein family, is significantly elevated in patients at the early stages of diffuse systemic sclerosis. Their findings suggest that BAG3 may play a dual role, not just as a biomarker, but potentially also in the pathogenesis of this disease.

Source:

Extracellular BAG3 is elevated in early diffuse systemic sclerosis

https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-025-00628-w

The new tool, published in Nature Biomedical Engineering, involves a synthetic protein called Crunch, short for Connector for Removal of Unwanted Cell Habitat. Crunch uses the body's natural waste removal system to clear out specific target cells, offering hope for improved treatments for cancer, autoimmune diseases, and other diseases where harmful cells cause damage.

Every day, billions of our body's cells naturally die as part of normal processes. These dead cells are quickly cleaned up by immune cells called phagocytes. Phagocytes act like microscopic vacuum cleaners, spotting dying cells by detecting an "eat me" signal on their surface. Once they recognize that signal, they surround and digest the dead cells in a process called "phagocytosis" or more specifically "efferocytosis."

"What we've done is take that natural cleaning system and reprogram it to target living cells that shouldn't be there,"

During times of human conflict, infections thrive among the wounded and overcrowded, and the surrounding environment is likely to become contaminated with heavy metals and unsafe water, which further propagates the spread of disease. Meanwhile, hospitals struggle to save lives with restricted resources (e.g., shortages of medical staff, medications and supplies), and people have difficulty accessing, or simply cannot access, health care if/when it is available.

In short, conflict fuels the uncontrolled spread of infections in environments where proper health care is hard to come by, which leads to misuse of antibiotics without proper diagnosis and treatment. This, in turn, allows pathogens to rapidly develop antimicrobial resistance (AMR).

Asbestosis is a type of fibrosis or scarring of the lungs caused by asbestos fibres which have been lodged in the lungs after inhalation. Fibrosis causes the lung to contract resulting in breathlessness.

Asbestosis particularly affects people who have breathed in substantial amounts of asbestos dust in the course of their work. It usually takes a long time to show after initial inhalation of the dust, as much as 20 or 30 years after exposure.

Once the scarring has begun, asbestosis is irreversible. Asbestosis victims can develop complications which can sometimes be fatal, such as heart disease and lung infections.

Last week, the Trump administration approved yet another delay in the implementation of a Mine Safety and Health Administration (MSHA) rule to lower miners’ exposure to deadly silica dust. The National Sand, Stone and Gravel Association sued to block the rule back in April—and instead of voicing any opposition to the suit or support for the rule, the Trump Labor Department has ignored the miners’ plight in favor of well-heeled corporate interests.