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Clinical research has long focused on ways to harness the actions of the immune system. From vaccines to immunotherapies, researchers have used their knowledge of the immune system to develop therapies to treat or prevent diseases from influenza to autoimmune disease and cancer.

Now, researchers from Penn’s School of Dental Medicine and international collaborators have investigated the effects of training the innate immune system in experimental models of two chronic inflammatory diseases, periodontitis and arthritis. They found that this “trained” immunity, or TRIM, led to increased bone loss in these models. This study is published in Developmental Cell.

Previous approaches have largely focused on the adaptive immune system, that branch of the immune system that “remembers” previous threats and launches specific attacks when it encounters them again. The body also has an innate immunity branch, which, for a long time, was just considered the first-line, general attack arm of the immune system with no ability to remember prior assaults or respond differently when rechallenged.

“If you go and look at an immunology textbook-even today-it will likely tell you that innate immunity has no memory; its response doesn’t get improved the second time,” says George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Basic & Translational Sciences at Penn Dental Medicine.

This belief, Hajishengallis notes, has been challenged over the past decade. Studies have shown that the innate immune system can respond more strongly when challenged again with the same or different stimulus-in other words, it can be “trained.”

And importantly, these studies have also shown that “training” the innate immune system has beneficial effects, such as anti-tumor activity and an increased response to fighting infections in certain experimental models.

But inflammation—the innate immune system’s natural response to harmful stimuli-can also exacerbate symptoms or even cause diseases, demonstrating the need to better understand the immune system when developing immune-based therapies. An increased response may not always be beneficial.

“Trained innate immunity (TRIM) has emerged as a major immunological principle that challenges the dogma that memory is restricted to adaptive immunity,” says Hajishengallis. “So, a better understanding of TRIM is imperative to appropriately harness it for therapeutic gain in human disease.”

The Hajishengallis team along with a collaborative lab led by Triantafyllos Chavakis at the Dresden University of Technology, induced TRIM using ß-glucan, a compound found in certain fungi, and measured the generation of osteoclasts, which resorb bone during growth and healing, in models of inflammatory periodontitis and arthritis.

“We found that this treatment primed osteoclast precursors to differentiate into osteoclasts more readily if presented with an inflammatory challenge like arthritis,” says Chavakis.

“So, although TRIM can have beneficial effects-protecting against infections and cancer-our results indicate that the memory of a previous infection may also contribute to inflammatory diseases and the comorbidity between inflammatory bone loss disorders,” adds Hajishengallis.

Their work, however, showed that ß-glucan only increases the opportunity for bone loss to occur-it does not cause actual bone loss. That only occurs if a second inflammatory stimulus, such as arthritis or periodontitis, is present.

“This requirement [for a secondary challenge] epitomizes the concept of trained immunity-the training stimulus causes a state of preparedness for future events,” says Hajishengallis.

Importantly, these results argue against the idea that it is the initial stimulus that is driving TRIM to be beneficial or maladaptive (harmful), as ß-glucan caused beneficial TRIM (for example, tumor growth inhibition) in previous studies by Hajishengallis and Chavakis.

“Our findings suggest that the context in which TRIM emerges dictates whether the functional outcome is protective or harmful,” says Chavakis.

“The double-edged sword nature of TRIM acquires special relevance when considering the preventive or therapeutic application of TRIM-inducing agents,” adds Hajishengallis.

Reference:

Nora Haacke, Hui Wang, Shu Yan, Marko Barovic, Xiaofei Li, Kosuke Nagai, Adelina Botezatu, Aikaterini Hatzioannou, Bettina Gercken, Giulia Trimaglio, Anisha U. Shah, Jun Wang, Ling Ye, Mangesh T. Jaykar, Martina Rauner, Ben Wielockx, Kyoung-Jin Chung, Mihai G. Netea, Lydia Kalafati, George Hajishengallis, Triantafyllos Chavakis, Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice, Developmental Cell, https://doi.org/10.1016/j.devcel.2025.02.001

Hormones may be leveraged to treat and prevent signs of aging such as wrinkles and hair graying, according to a new study published in the Endocrine Society journal Endocrine Reviews.

Until now, only a limited number of hormones, mainly topical retinoids (retinol and tretinoin) and estrogen which is typically used to treat side effects of menopause, have been used in clinical practice as anti-skin aging compounds. This study reviews a new class of hormones and their anti-aging properties.

“Our paper highlights key hormone players that orchestrate pathways of skin aging such as degradation of connective tissue (leading to wrinkling), stem cell survival and loss of pigment (leading to hair graying),” said lead author Markus Böhm, M.D., of the University of Münster in Münster, Germany. “Some of the hormones we studied have anti-aging properties and may be used in the future as agents to prevent skin aging.”

The skin is the largest organ and undergoes both intrinsic (chronological) and extrinsic aging which is caused by environmental factors such as sun exposure.

“Skin is not only a target for various hormones that control pathways of skin aging but itself is certainly the largest and richest site for hormone production besides classical endocrine glands,” Böhm said.

To better understand the connection between hormones and skin aging, the researchers studied the pivotal hormones controlling skin aging, including insulin-like growth factor 1, growth hormone, estrogens, retinoids and melatonin. Melatonin is especially interesting as a potential anti-skin aging substance as it is a small molecule, inexpensive, well-tolerated and a direct and indirect antioxidant as well as a regulator of mitochondrial metabolism. Some of the studied hormones, moreover, have astonishing and unexpected biological effects on skin function and hair aging as highlighted by distinct genetic deficiency syndromes.

They also reviewed the emerging roles of additional endocrine players, including α-melanocyte-stimulating hormone (responsible for skin pigmentation), members of the hypothalamic-pituitary-thyroid axis, oxytocin, endocannabinoids (found in CBD products) and peroxisome proliferator-activated receptor modulators and found they have very promising effects, e.g. on UV-induced genotoxic stress crucially involved in the development of photoaging and pigment synthesis within skin and hair.

“Further research into these hormones may offer opportunities to develop new therapeutics for treating and preventing skin aging,” Böhm said.

Other study authors are Agatha Stegemann and Konrad Kleszczyński of the University of Münster; Ralf Paus of the University of Miami Leonard M. Miller School of Medicine in Miami, Fla., the University of Manchester in Manchester, U.K., and CUTANEON – Skin & Hair Innovations in Hamburg & Berlin, Germany; and Pallab Maity, Meinhard Wlaschek and Karin Scharffetter-Kochanek of Ulm University in Ulm, Germany.

The researchers received funding from the Deutsche Forschungsgemeinschaft, the University of Miami Leonard M. Miller School of Medicine, the International Graduate School in Molecular Medicine Ulm, and the Medizinische Fakultät, Universität Ulm.

A new study published in the journal of Therapeutic Advances in Respiratory Disease showed that after just 4 to 8 weeks, pulmonary rehabilitation (PR), which includes breath control exercises, can help long-term COVID patients’ lung function.

According to the World Health Organization (WHO), long-lasting COVID-19 symptoms are those that appear more than three months after infection or are more severe than pre-COVID-19 symptoms and last for at least 2 months without a known cause. Originally created to treat chronic obstructive pulmonary disease (COPD), pulmonary rehabilitation is now acknowledged as a fundamental therapy strategy for a number of chronic cardiopulmonary disorders.

Based mostly on expert opinion and observational evidence, WHO and the European Respiratory Society/American Thoracic Society recommendations also suggested PR for the treatment of prolonged COVID-19 symptoms. Thus, this study was carried out to compare the effectiveness of various PR intervention kinds and durations as well as to assess the effect of PR on patients with prolonged COVID-19.

This study included randomized controlled trials (RCTs) published prior to April 2024 that examined the efficacy of PR in long-term COVID-19 patients. The 6-minute walking test (6MWT), lung function as determined by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), tiredness, and health-related quality of life (HRQoL) were the main outcomes. maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), handgrip strength tests, the 30-second sit-to-stand test (30STST), dyspnea, depression, anxiety, perceived exertion, and adverse events were secondary outcomes.

There were 37 trials with 3363 individuals in all. PR did not approach statistical significance for depression, but it did enhance physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, tiredness, dyspnea, and anxiety when compared to controls.

Programs lasting less than four weeks improved 6MWT, those lasting four to eight weeks substantially improved 6MWT, lung function (FEV1, FVC), HRQoL, and decreased tiredness, while programs lasting more than eight weeks enhanced HRQoL and decreased fatigue, according to subgroup analyses of PR length.

Breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL, according to exercise type analysis; multicomponent exercises increased 6MWT performance and decreased tiredness; and combining the two kinds improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and decreased fatigue.

Overall, in long-term COVID-19 patients, PR reduces anxiety, exhaustion, and dyspnea while also improving physical capacity, lung function, and quality of life. Long-term COVID-19 disorders are best managed with a 4- to 8-week PR program that combines multicomponent training with breath exercises.

Source:

Li, S., Dai, B., Hou, Y., Zhang, L., Liu, J., Hou, H., Song, D., Wang, S., Li, X., Zhao, H., Wang, W., Kang, J., & Tan, W. (2025). Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials. Therapeutic Advances in Respiratory Disease, 19. https://doi.org/10.1177/17534666251323482

Italy: Researchers have found in new research that free flap surgery with dual innervation for long-term paralysis of the lower third of the face can achieve comparable results using either latissimus dorsi or gracilis free flaps. Further, the optimal choice depends on individual cases, considering the surgeon’s expertise, the patient’s preferences, and overall expectations.