Biological Dysfunction Research Articles

Engineering biocompatible carbon dots nano-enzymes hydrogel for efficient antioxidative and anti-inflammatory treatment of dry eye disease.

Dry eye disease (DED) is a complex and multifactorial ocular surface disease. Reactive oxygen species (ROS) are of pivotal importance in the inflammatory processes and biological dysfunction associated with DED. In this study, an injectable hydrogel, designated as OHACDgel, was created by combining oxidized HA-containing aldehyde groups (OHA) and gelation (gel) via dynamic covalent linkages of the hydrazine bonds, is employed as the carrier, while polyethylene imine-functionalized carbon dots (PEI-CD) can form dynamic chemical bonds with the hydrogel, thus prolonging the retention time of the ocular. OHACDgel has been demonstrated to markedly diminish ROS overproduction, reduce the expression of pro-inflammatory factors, inhibit the transformation of macrophages into a pro-inflammatory phenotype, reverse corneal epithelial defects, restore goblet cell function, and enhance tear secretion. Furthermore, the biocompatibility of OHACDgel has been demonstrated, presenting a rapid and straightforward therapeutic option for potential applications in DED.

Behavioral problems in children with unoperated rheumatic heart disease at national referral hospital in Ethiopia: an observational study

BackgroundThe behavioral disorder is characterized by a profound abnormality in an individual’s cognition, emotion or behavior that reflects in psychological, biological or developmental dysfunction. Rheumatic heart disease (RHD) is a long-term sequel of single or recurrent acute rheumatic fever. Children with RHD are thought to be at increased risk for behavioral problems due to autoimmunity seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Behavior disorder is not well studied among children with RHD. Hence, this study aimed to assess the pattern and predictors of behavioral problems among children with RHD enrolled in chronic care at a national cardiac referral Hospital.MethodsThis cross-sectional study used a validated parental-reported Amharic Strengths and Difficulties Questionnaire (SDQ) to assess behavior problems. Children with RHD aged 6–17 years on chronic outpatient cardiac care at Tikur Anbessa Specialized Hospital, Ethiopia between February and May 2023 were included. Factors associated with behavior problems were assessed using logistic regression models.ResultsThe study included 166 children with a median age of 15 years [Interquartile range (IQR):13–17 years]. One-fourth of children, 24.7% (95% CI: 18.34–31.98), had behavioral problems. Of these, 46.4% (77) emotional, 35.5% (59) peer, 18.1% (30) conduct and 6.6% (11) hyperactivity problems were documented. Children who had good medication adherence, adjusted odds ratio AOR 0.29(95% CI: 0.09–0.94, P 0.040) and on New York Health Association (NYHA) class I, AOR 0.28(95% CI: 0.11–0.79, P 0.016) had lower odds for behavioral problems.ConclusionOne-fourth of children with RHD had behavioral abnormalities. Medication adherence and NYHA predicted behavioral abnormality. Better physical symptom control was associated with fewer behavioral problems. Behavioral abnormalities should be considered and assessed among children with RHD. Further multi-center mixed studies are recommended to uncover the unseen behavioral problem and guide health policy action on modalities of integration of behavioral problems assessment tools in clinical care.

Porphyromonas gingivalis inducing autophagy-related biological dysfunction in alveolar epithelial cells: an in vitro study

BackgroundChronic obstructive pulmonary disease (COPD) is a respiratory disease with high morbidity and mortality. Notably, the pathogenesis and progression of COPD are related to lung infection, inflammatory response, and biological dysfunction in alveolar epithelial cells. Studies also found that periodontitis is an independent risk factor for COPD. The inhalation of periodontal pathogens into the respiratory system is the most common method for periodontal pathogens to promote the development of COPD. Porphyromonas gingivalis (P. gingivalis), the keystone pathogen in periodontitis, has been found to migrate to the lungs, triggering inflammatory reactions and causing decreased lung function. However, the impact of P. gingivalis infection on the biological function of alveolar epithelial cells remains unclear. Therefore, this study aimed to investigate the effects of P. gingivalis infection on the biological functions of alveolar epithelial cells.MethodsMouse alveolar epithelial cells (MLE-12) were co-cultured with P. gingivalis and treated with autophagy inhibitor chloroquine (CQ) or LC3 siRNA in vitro. MTT assay and EdU staining were used to detect cell viability, and the TUNEL assay kit and Annexin V-FITC/PI method were used to detect cell apoptosis. Western blot was used to detect autophagic markers LC3 and P62, and mRFP-GFP-LC3 was used to observe autophagic flux.ResultsP. gingivalis inhibited the viability of alveolar epithelial cells in a dose- and time-dependent manner. P. gingivalis also promoted autophagy and apoptosis of alveolar epithelial cells in a dose-dependent manner. Interestingly, we found that inhibiting autophagy using CQ or silencing LC3 with siRNA significantly reduced cell apoptosis and viability damage induced by P. gingivalis. Thus, these data indicated the synergistic effect of autophagy in P. gingivalis-induced biological dysfunction of alveolar epithelial cells.ConclusionP. gingivalis infection can cause biological dysfunction of alveolar epithelial cells, manifested as decreased cell viability, increased autophagy and apoptosis. Notably, the up-regulation of autophagy induced by P. gingivalis plays a synergistic role in this dysfunction.

Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes

Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.

Rethinking the Complexities of the Body and Disability: Theological Account

The biological aspect of human embodiment frequently constitutes the primary basis for personal assessment, with an emphasis on rationality, free choice, material well-being, and happiness as fundamental attributes of worth. This perspective is also evident in cultural practices of body modification, which reflect societal standards and identity expression. The promotion of standards of bodily appearance that are often considered unrealistic within contemporary culture has the effect of creating a social environment in which those who do not conform to these standards are rejected and stigmatized. This can include individuals with disabilities, the elderly, or those with chronic illnesses and different bodily appearances. In the majority of cases, the so-called ‘body capital’ culture views the disabled body through the lens of a person’s physical appearance, which is, to a certain extent, associated with a biological dysfunction or reflects a kind of physical disability or vulnerable corporeality. This paper seeks to examine perspectives on the body through the lenses of major discourses surrounding disability, biblical anthropology, and disability theology. These perspectives advocate for the intrinsic dignity and value of the disabled body, challenging contemporary norms and projections upon the body, by underscoring the biographical, interdependent, and spiritual dimensions of human embodiment. This approach stands as an alternative to the reductionist view of the body, which prioritizes physical attributes over a comprehensive understanding of complete personhood.

Single-molecule digital sizing of proteins in solution

The physical characterization of proteins in terms of their sizes, interactions, and assembly states is key to understanding their biological function and dysfunction. However, this has remained a difficult task because proteins are often highly polydisperse and present as multicomponent mixtures. Here, we address this challenge by introducing single-molecule microfluidic diffusional sizing (smMDS). This approach measures the hydrodynamic radius of single proteins and protein assemblies in microchannels using single-molecule fluorescence detection. smMDS allows for ultrasensitive sizing of proteins down to femtomolar concentrations and enables affinity profiling of protein interactions at the single-molecule level. We show that smMDS is effective in resolving the assembly states of protein oligomers and in characterizing the size of protein species within complex mixtures, including fibrillar protein aggregates and nanoscale condensate clusters. Overall, smMDS is a highly sensitive method for the analysis of proteins in solution, with wide-ranging applications in drug discovery, diagnostics, and nanobiotechnology.

Unraveling the Complexity: Psychiatric Diagnoses and Character Attributes

This paper explores the complex relationship between mental illness and character flaws, using the Lorena Bobbitt case as a starting point to challenge the notion that these two concepts are synonymous. By defining mental illness as a biological dysfunction and character flaws as maladaptive behaviors rooted in social contexts, this essay distinguishes between the two. It examines their causes, diagnostic methods, treatments, and implications in the legal system. The analysis highlights the importance of differentiating between mental illness and character flaws to ensure fair treatment and effective intervention within both clinical and legal frameworks.

Molecular dynamics simulation on regulation of liquid–liquid phase separation of repetitive peptides

Understanding the intricate interactions governing protein and peptide behavior in liquid–liquid phase separation (LLPS) is crucial for unraveling biological functions and dysfunctions. This study employs a residue-leveled coarse-grained molecular dynamics approach to simulate the phase separation of repetitive polyproline and polyarginine peptides (poly PR) with varying lengths and sequences in solution, considering different concentrations and temperatures. Our findings highlight the crucial role of sequence order in promoting LLPS in peptides with identical lengths of repetitive sequences. Interestingly, repetitive peptides containing fewer than 10 polyarginine repeats exhibit no LLPS, even at salt concentrations up to 3 M. Notably, our simulations align with experimental observations, pinpointing a salt concentration of 2.7 M for PR25-induced LLPS. Utilizing the same methodology, we predict the required salt concentrations for LLPS induction as 1.2 M, 1.5 M, and 2.7 M for PR12, PR15, and PR35, respectively. These predictions demonstrate good agreement with experimental results. Extending our investigation to include the peptide glutamine and arginine (GR15) in DNA solution, our simulations mirror experimental observations of phase separation. To unveil the molecular forces steering peptide phase separation, we introduce a dielectric constant modifier and hydrophobicity disruptor into poly PR systems. Our coarse-grained analysis includes an examination of temperature effects, leading to the inference that both hydrophobic and electrostatic interactions drive phase separation in peptide systems.

Intermittent fasting, exercise, and dietary modification induce unique transcriptomic signatures of multiple tissues governing metabolic homeostasis during weight loss and rebound weight gain

Obesity and its related metabolic diseases bring great challenges to public health. In-depth understanding on the efficacy of weight-loss interventions is critical for long-term weight control. Our study demonstrated the comparable efficacy of exercise (EX), intermittent fasting (IF), or the change of daily diet from an unhealthy to a normal chow (DR) for weight reduction, but largely divergently affected metabolic status and transcriptome of subcutaneous fat, scapular brown fat, skeletal muscles and liver in high-fat-high-fructose diet (HFHF) induced obese mice. EX and IF reduced systematic inflammation, improved glucose and lipid metabolism in liver and muscle, and amino acid metabolism and thermogenesis in adipose tissues. EX exhibited broad regulatory effects on TCA cycle, carbon metabolism, thermogenesis, propanoate-, fatty acid and amino acid metabolism across multiple tissues. IF prominently affected genes involved in mitophagy and autophagy in adipose tissues and core genes involved in butanoate metabolism in liver. DR, however, failed to improve metabolic homeostasis and biological dysfunctions in obese mice. Notably, by exploring potential inter-organ communication, we identified an obesity-resistant-like gene profile that were strongly correlated with HFHF induced metabolic derangements and could predict the degree of weight regain induced by the follow-up HFHF diet. Among them, 12 genes (e.g., Gdf15, Tfrc, Cdv3, Map2k4, and Nqo1) were causally associated with human metabolic traits, i.e., BMI, body fat mass, HbA1C, fasting glucose, and cholesterol. Our findings provide critical groundwork for improved understanding of the impacts of weight-loss interventions on host metabolism. The identified genes predicting weight regain may be considered regulatory targets for improving long-term weight control.

Biological functions and dysfunctions: a selected dispositions approach

Justin Garson has recently argued that proper functions are proximal activities of traits selected by phylogenetic or ontogenetic selection processes, and that traits are dysfunctional only if they cannot perform their proper functions for constitutional reasons. We partially agree with Garson, but reject the view that functions are proximal activities, as well as his account of dysfunctions. Instead, we propose our own theory that biological functions are selected dispositions and that a trait is dysfunctional in virtue of not having the dispositions for which it was selected. This account can explain both defects (or dysfunctions in Garson’s sense) and dysfunctions due to environmental factors. Moreover, it offers a neat way to explain the graduality of dysfunction.

High glucose regulates the cells dysfunction of human trophoblast HTR8/SVneo cells by downregulating GABRP expression.

In response to the high-glucose environment in patients with gestational diabetes mellitus (GDM), trophoblast cells undergo a series of pathological changes. Gamma-aminobutyric acid type A receptor subunit pi (GABRP) is involved in the development of pregnancy-related diseases and regulation of blood glucose. To explore the relationship between GABRP and hyperglycemia stimulation in GDM patients, and to provide preliminary experimental evidence for whether GABRP has the potential as a molecular target for the treatment of GDM. Within 30 min after birth, placental samples were taken from 20 GDM patients and 20 pregnant women without GDM. Human chorionic trophoblast HTR-8/SVneo cells were utilized for in vitro experimental investigation. We explored changes in GABRP expression in placental samples and HTR-8/Svneo cells using western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cells in the high-glucose treatment group were exposed to medium containing 25 mM glucose. To explore the relationship between GABRP and high-glucose stimulation, GABRP was overexpressed in HTR-8/SVneo cells. We monitored the cell viability, invasion and migration abilities using Cell Counting Kit-8 (CCK-8), transwell and scratch assays, respectively. We found that GABRP expression was significantly reduced in placental samples from GDM patients. Furthermore, high-glucose treatment decreased the expression level of GABRP in HTR-8/SVneo cells. High-glucose stimulation reduced the cell viability, invasion and migration abilities. GABRP overexpression reversed the biological dysfunction of the cells induced by high-glucose stimulation. Hyperglycemia in GDM patients downregulates the expression of GABRP, and overexpression of GABRP promotes the viability, migration and invasive ability of HTR8-/SVneo cells.

Genomic analysis of fibroblasts from marmosets carrying early‐onset Alzheimer’s disease mutations in PSEN1

AbstractBackgroundAlzheimer’s disease (AD) is the most prevalent form of dementia and remains generally untreatable. The slow, age‐related development of AD and inaccessibility of early‐stage brain tissue has limited our understanding of its origins and progression. Large‐scale genetic studies and molecular analysis of postmortem brain samples have nominated dozens of candidate genes and proteins for therapeutic targeting or diagnostic biomarkers, generating a need for in vivo systems to study the underlying biological dysfunction and perform preclinical testing. Here, we report on genetic, genomics, and proteomic analysis of fibroblast lines derived from a colony of marmosets genetically engineered with rare familial variants in the PSEN1 gene.MethodWe performed whole‐genome sequencing on 14 individuals, including six mutant carriers. We validated the presence of the PSEN1 mutations and assessed variation at multiple other Alzheimer’s disease loci. Fibroblast cultures were obtained from 12 animals and assayed using a Nanostring AD gene expression panel and label‐free proteomics. This allowed us to quantify 800 transcripts and 2165 proteins per sample.ResultWe detected differential gene expression for genes enriched in neuron development and amyloid‐beta regulation, providing strong evidence for the functional relevance of the engineered variants. We quantitatively compared changes in marmoset PSEN1 fibroblasts to similar molecular measures in postmortem brain tissue and induced pluripotent stem cells (iPSCs) from human AD studies. Both gene and protein expression changes in the undifferentiated fibroblasts correlated with changes in iPSCs from human AD carriers reprogrammed into neuronal lineages. We also observed both transcriptomic and proteomic changes in marmoset PSEN1 cells that match those in postmortem AD brains.ConclusionThese findings demonstrate that disease‐relevant pathways and processes are altered in fibroblasts from mutant marmosets, provide a roadmap for more advanced molecular studies of AD in aging marmosets and marmoset‐derived cell models, and outline a strategy to align marmoset models with human disease to facilitate robust translation.

The first genomic characterization of a stable, hemin-dependent small colony variant strain of Staphylococcus epidermidis isolated from a prosthetic-joint infection

Phenotype switching from a wild type (WT) to a slow-growing subpopulation, referred to as small colony variants (SCVs), supports an infectious lifestyle of Staphylococcus epidermidis, the leading cause of medical device-related infections. Specific mechanisms underlying formation of SCVs and involved in the shaping of their pathogenic potential are of particular interest for stable strains as they have been only rarely cultured from clinical specimens. As the SCV phenotype stability implies the existence of genetic changes, the whole genome sequence of a stable, hemin-dependent S. epidermidis SCV strain (named 49SCV) involved in a late prosthetic joint infection was analyzed. The strain was isolated in a monoculture without a corresponding WT clone, therefore, its genome was compared against five reference S. epidermidis strains (ATCC12228, ATCC14990, NBRC113846, O47, and RP62A), both at the level of the genome structure and coding sequences. According to the Multilocus Sequence Typing analysis, the 49SCV strain represented the sequence type 2 (ST2) regarded as the most prominent infection-causing lineage with a worldwide dissemination. Genomic features unique to 49SCV included the absence of the Staphylococcal Cassette Chromosome (SCC), ~12 kb deletion with the loss of genes involved in the arginine deiminase pathway, and frameshift-generating mutations within the poly(A) and poly(T) homopolymeric tracts. Indels were identified in loci associated with adherence, metabolism, stress response, virulence, and cell wall synthesis. Of note, deletion in the poly(A) of the hemA gene has been considered a possible trigger factor for the phenotype transition and hemin auxotrophy in the strain. To our knowledge, the study represents the first genomic characterization of a clinical, stable and hemin-dependent S. epidermidis SCV strain. We propose that previously unreported indels in the homopolymeric tracts can constitute a background of the SCV phenotype due to a resulting truncation of the corresponding proteins and their possible biological dysfunction. Streamline of genetic content evidenced by the loss of the SCC and a large genomic deletion can represent a possible strategy associated both with the SCV phenotype and its adaptation to chronicity.

Direct observation of glycans bonded to proteins and lipids at the single-molecule level.

Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical strategies for these glycan-decorated biomolecules, termed glycoconjugates, rely on ensemble-averaged methods that do not provide a full view of positions and structures of glycans attached at individual sites in a given molecule, especially for glycoproteins. We show single-molecule analysis of glycoconjugates by direct imaging of individual glycoconjugate molecules using low-temperature scanning tunneling microscopy. Intact glycoconjugate ions from electrospray are soft-landed on a surface for their direct single-molecule imaging. The submolecular imaging resolution corroborated by quantum mechanical modeling unveils whole structures and attachment sites of glycans in glycopeptides, glycolipids, N-glycoproteins, and O-glycoproteins densely decorated with glycans.

Exploring Associations Between Abnormal Weight Classifications and Child Maltreatment Diagnoses.

Child maltreatment poses not only immediate danger, but as a type of toxic stress, it creates higher risk of biologic dysfunction later in life. Pediatricians are in a unique position to diagnose child maltreatment, but they need evidence-based guidance for when to initiate screening when injury is occult. In this retrospective cohort study of 855 pediatric patients diagnosed with child maltreatment, researchers explored whether type or number of diagnoses was associated with abnormal pediatric weight in either direction. Diagnoses and weight assessed at intake were extracted from medical records for analysis. Statistically significant associations were found between weight classification and child maltreatment type as well as diagnosis count. Neglect was most frequently diagnosed, and children with ≥2 diagnoses were more likely to be classified as underweight, overweight, or obese. Findings support abnormal pediatric weight as a biologic signal of adversity that warrants safety screening in the clinical setting.

Frailty syndrome and associated factors among patients with hypertension: A cross-sectional study in Kumasi, Ghana.

Frailty is a condition marked by accumulation of biological deficits and dysfunctions that come with aging and it is correlated with high morbidity and mortality in patients with cardiovascular diseases, particularly hypertension. Hypertension continues to be a leading cause of cardiovascular diseases and premature death globally. However, there is dearth of literature in sub-Saharan Africa on frailty syndrome among hypertensives on medication. This study evaluated frailty syndrome and its associated factors among Ghanaian hypertensives. This cross-sectional study recruited 303 patients with hypertension from the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Data on sociodemographic, lifestyle and clinical factors were collected using a well-structured questionnaire. Medication adherence was measured using Adherence in Chronic Disease Scale, and frailty was assessed by Tilburg Frailty Indicator. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism 8.0. p-value of < 0.05 and 95% confidence interval (CI) were considered statistically significant. The prevalence of frailty was 59.7%. The proportion of high, medium and low medication adherence was 23.4%, 64.4% and 12.2%, respectively. Being ≥ 70years (adjusted odds ratio [aOR]: 8.33, 95% CI [3.72-18.67], p < 0.0001), unmarried (aOR: 2.59, 95% CI [1.37-4.89], p = 0.0030), having confirmed hypertension complications (aOR: 3.21, 95% CI [1.36-7.53], p = 0.0080), medium (aOR: 1.99, 95% CI [1.05-3.82], p = 0.0360) and low antihypertensive drug adherence (aOR: 27.69, 95% CI [7.05-108.69], p < 0.0001) were independent predictors of increased odds of developing frailty syndrome. Approximately 6 out of 10 Ghanaian adult patients with hypertension experience frailty syndrome. Hypertension complications, older age, being unmarried, and low antihypertensive drug adherence increased the chances of developing frailty syndrome. These should be considered in intervention programmes to prevent frailty among patients with hypertension.

Movement Disorders in Patients With Genetic Developmental and Epileptic Encephalopathies.

Movement disorders (MDs) are underrecognized in the developmental and epileptic encephalopathies (DEEs). There are now more than 800 genes implicated in causing the DEEs; relatively few of these rare genetic diseases are known to be associated with MDs. We identified patients with genetic DEEs who had MDs, classified the nature of their MDs, and asked whether specific patterns correlated with the underlying mechanism. We classified the type of MDs associated with specific genetic DEEs in a large international cohort of patients and analyzed whether specific patterns of MDs reflected the underlying biological dysfunction. Our cohort comprised 77 patients with a genetic DEE with a median age of 9 (range 1-38) years. Stereotypies (37/77, 48%) and dystonia (34/77, 44%) were the most frequent MDs, followed by chorea (18/77, 23%), myoclonus (14/77, 18%), ataxia (9/77, 12%), tremor (7/77, 9%), and hypokinesia (6/77, 8%). In 47% of patients, a combination of MDs was seen. The MDs were first observed at a median age of 18 months (range day 2-35 years). Dystonia was more likely to be observed in nonambulatory patients, while ataxia was less likely. In 46% of patients, therapy was initiated with medication (34/77, 44%), deep brain stimulation (1/77, 1%), or intrathecal baclofen (1/77, 1%). We found that patients with channelopathies or synaptic vesicle trafficking defects were more likely to experience dystonia; whereas, stereotypies were most frequent in individuals with transcriptional defects. MDs are often underrecognized in patients with genetic DEEs, but recognition is critical for the management of these complex neurologic diseases. Distinguishing MDs from epileptic seizures is important in tailoring patient treatment. Understanding which MDs occur with different biological mechanisms will inform early diagnosis and management.

An account of medical treatment, with a preliminary account of medical conditions.

In this article, I present a philosophical account of medical treatment. In support of this account, I offer a suggestive account of medical conditions. The account of medical treatment uses three desiderata to demarcate treatment from non-treatment. Namely, a treatment should: (1) be describable by features that enable it to be standardized and characterized as a discrete intervention, (2) target a specific medical condition, and (3) have the possibility of being effective. The account of medical conditions underlies the second desideratum and attempts to tie medical conditions closely to biological dysfunction, while also including some conditions for which biological dysfunction is absent or its presence uncertain. I offer a simple typology of treatments and show how the accounts are relevant to treatment effectiveness, disease, placebos, contested treatments, and treatment standardization.

Biomimetic Protocells Featuring Macrophage-Like Capture and Digestion of Protein Pathogens.

Modern medical research develops interest in sophisticated artificial nano- and microdevices for future treatment of human diseases related to biological dysfunctions. This covers the design of protocells capable of mimicking the structure and functionality of eukaryotic cells. The authors use artificial organelles based on trypsin-loaded pH-sensitive polymeric vesicles to provide macrophage-like digestive functions under physiological conditions. Herein, an artificial cell is established where digestive artificial organelles (nanosize) are integrated into a protocell (microsize). With this method, mimicking crossing of different biological barriers, capture of model protein pathogens, and compartmentalized digestive function are possible. This allows the integration of different components (e.g., dextran as stabilizing block) and the diffusion of pathogens in simulated cytosolic environment under physiological conditions. An integrated characterization approach is carried out, with identifying electrospray ionization mass spectrometry as an excellent detection method for the degradation of a small peptide such as β-amyloid. The degradation of model enzymes is measured by enzyme activity assays. This work is an important contribution to effective biomimicry with the design of cell-like functions having potential for therapeutic action.

Epistemic injustice, naturalism, and mental disorder: on the epistemic benefits of obscuring social factors

Naturalistic understandings that frame human experiences and differences as biological dysfunctions have been identified as a key source of epistemic injustice. Critics argue that those understandings are epistemically harmful because they obscure social factors that might be involved in people’s suffering; therefore, naturalistic understandings should be undermined. But those critics have overlooked the epistemic benefits such understandings can offer marginalised individuals. In this paper, I argue that the capacity of naturalistic understandings to obscure social factors does not necessarily cause epistemic injustice and can even help people to avoid some epistemic injustice. I do this by considering how some individuals with bipolar disorder deploy the neurobiological understanding of their disorder, highlighting three functions it fills for them: explanation, disclamation, and decontestation. In performing these functions, the neurobiological understanding does marginalise alternative, social perspectives on bipolar disorder. However, this can be understood as a feature rather than a bug. By marginalising alternative explanations, the neurobiological understanding can help individuals with bipolar disorder resist epistemic injustice, including, for example, the trivialisation of their experiences. Given this, critics seeking to undermine naturalistic understandings of mental disorder and other experiences in the pursuit of epistemic justice themselves risk exacerbating epistemic injustice.