Prognostic Role of OX40, LAG-3, TIM-3 and PD-L1 Expression in Bone and Soft Tissue Sarcomas.

Introduction: The current study aims to evaluate the OX40, TIM-3, LAG-3, and PD-L1 targeted pathways in the regulation of T-cell activity in sarcoma patients to determine their relationship with overall survival (OS). Method: This study included one hundred and eleven patients with bone and soft tissue sarcoma diagnosed in two centers between 2010 and 2020. OX40, LAG-3, TIM-3 and PD-L1 expression levels were evaluated immunohistochemically from pathology preparations. Results: PD-L1 staining was detected in tumor cells, OX40, LAG-3, TIM-3 staining was detected in inflammatory cells in tumor tissue. In univariate analysis, no significant relationship was found between OX40, TIM-3, LAG-3, and PD-L1 staining and overall survival (respectively: p = 0.12, p = 0.49, p = 0.31, p = 0.95). When grade and stage at diagnosis, which were found to be significant in univariate analysis, along with OX-40, TIM-3, LAG-3, and PD-L1, were evaluated in multivariate analysis, a positive effect of OX-40 staining on overall survival was determined (p = 0.009). Considering the correlation between PDL-1 and OX40, TIM-3, and LAG-3 staining, a significant positive correlation was found between PDL-1 and TIM-3 and LAG-3 staining (respectively; p = 0.002, p = 0.001). Conclusions: There was no significant relationship between the PDL-1 staining percentage of tumor cells and OX40, TIM-3, and LAG-3 staining in inflammatory cells with the OS of sarcoma patients. However, detecting a significant positive correlation between PDL-1 staining and TIM-3 and LAG-3 staining also holds promise for finding effective targetable combination therapies that can prolong survival in sarcoma patients in the future.

A metagenomic survey of bacterial communities from kurut: The fermented cow milk in Kyrgyzstan.

Kurut is a traditional dry dairy product mostly consumed in Central Asia. In this study, the distribution of the dominant bacteria present in kurut samples (n=84) originated from seven (Chuy, Issyk-Kul, Talas, Naryn, Jalal-Abad, Osh, and Batken) regions in Kyrgyzstan were analyzed with Illumina iSeq100 platform. The dominant phylum detected was Firmicutes followed by Proteobacteria, Actinobacteria, Cyanobacteria/Chloroplast, and Tenericutes. The most abundant family detected was Lactobacillaceae followed by Streptococcaceae, Enterococcaceae, Chloroplast, and Leuconostocaceae. At the genus level, Lactobacillus was the predominant one in samples and Streptococcus, Enterococcus, Lactococcus, and Streptophyta followed this. Further comprehensive characterization analyses in kurut samples may have potential applications both in industrial starter culture developments and also future therapeutic approaches based on potential strains with probiotic properties.

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

BACKGROUND/PURPOSE: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. METHODS: The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. RESULTS: This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). CONCLUSION: According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Antioxidant Activity and Protective Effects of an Oxovanadium (IV) Complex on Heart and Aorta Injury of STZ-Diabetic Rats.

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.

Morphological and functional trait divergence in endemic fish populations along the small-scale karstic stream.

BACKGROUND: Organisms with broad distribution ranges, such as fish, often exhibit local ecological specializations based on their utilization of food and habitat. Populations of species that live in different habitat types (lotic vs. lentic) show morphological variations. However, the phenotypic differences of endemic fish populations in a small karst river basin under anthropogenic pressure are still not fully understood. In this study, the functional traits and morphological variations of the populations of endemic Pseudophoxinus antalyae Bogutskaya, 1992, in the Düden Stream basin, which is subjected to various anthropogenic disturbances and habitat types in southwestern Anatolia of Türkiye, were examined using linear measurements and geometric morphometric analysis. RESULTS: Differences have been identified in functional traits, particularly those related to food acquisition between populations. Results of both univariate and multivariate analyses revealed significant differences in body shape and size among populations living at sites along the stream with different habitat and environmental characteristics. CONCLUSIONS: The reason for these differences determined in the morphology and traits of the populations may depend on habitat types, ecological, or environmental, and obstruction of gene flow. More detailed studies are needed to explain the mechanisms (genetic and ecological) that cause these differences.

Biological therapy management from the initial selection of biologics to switching between biologics in severe asthma.

The aim of this review is to elaborate the management of biologic therapy from initial selection to switching biologics in severe asthma. A nonsystematic review was performed for biological therapy management in severe asthma. Depending on clinical characteristics and biomarkers, selecting the preferred biologic based on super-responder criteria from previous studies may result in adequate clinical efficacy in most patients. On the other hand, no matter how carefully the choice is made, in some patients, it may be necessary to discontinue the drug due to suboptimal clinical response or even no response. This may result in the need to switch to a different biological therapy. How long the biological treatment of patients whose asthma is controlled with biologics will be continued and according to which criteria they will be terminated remains unclear. It has been shown that in patients with a long history of good response to biologics, asthma control may be impaired when biologics are discontinued, while it may persist in others. Therefore, discontinuation of biologics may be a viable strategy in a particular patient group. Clinicians should make the best use of all predictive factors to identify patients who will most benefit from each biologic. Patients who do not meet a predefined response criterion after sufficient time for response evaluation and who are eligible for one or more alternative biological agents should be offered the opportunity to switch to another biologic. There is no consensus on when the biologics used in severe asthma that produce favorable results should be discontinued. In our opinion, treatment should continue for at least five years, as premature termination may potentially deteriorate asthma control.

Determination of Bacterial Diversity of Propolis Microbiota.

Propolis is a natural resinous mixture produced by the excretions of honeybees. PCR amplification of the 16S rRNA gene region was achieved using DNA of pre-enriched propolis samples collected from Apis mellifera production hives (n=37) in Eastern Türkiye (Bingöl and its regions). Next-generation sequencing and metabarcoding techniques were used to identify bacterial communities in propolis samples. Firmicutes dominated the phylum structure, with Proteobacteria, Actinobacteria, Tenericutes, and Spirochaetes following. The top three bacterial families were Bacillaceae, Enterobacteriaceae, and Enterococcaceae. Bacillus (dominantly B. badius and B. thermolactis at the species level) was recognized at the genus level, followed by Enterococcus and Clostridium sensu stricto. Our study comprehensively identified the bacterial diversity of propolis samples. Further investigations targeting to enlighten the microbiota of propolis and its potential application fields are required to gain better insight into ecological, nutritional, and medicinal perspectives.

A time-heterogeneous D-vine copula model for unbalanced and unequally spaced longitudinal data.

In many longitudinal studies, the number and timing of measurements differ across study subjects. Statistical analysis of such data requires accounting for both the unbalanced study design and the unequal spacing of repeated measurements. This paper proposes a time-heterogeneous D-vine copula model that allows for time adjustment in the dependence structure of unequally spaced and potentially unbalanced longitudinal data. The proposed approach not only offers flexibility over its time-homogeneous counterparts but also allows for parsimonious model specifications at the tree or vine level for a given D-vine structure. It further provides a robust strategy to specify the joint distribution of non-Gaussian longitudinal data. The performance of the time-heterogeneous D-vine copula models are evaluated through simulation studies and by a real data application. Our findings suggest improved predictive performance of the proposed approach over the linear mixed-effects model and time-homogeneous D-vine copula model.

Tumor-Infiltrating Lymphocytes (TIL), Tertiary Lymphoid Structures (TLS), and Expression of PD-1, TIM-3, LAG-3 on TIL in Invasive and In Situ Ductal Breast Carcinomas and Their Relationship with Prognostic Factors.

INTRODUCTION: Immunotherapy has been determined as an important choice in breast carcinomas, especially in tumors with markedly inflammatory response. About this promising subject, tumor-infiltrating lymphocytes (TIL) and the expression of immune control point receptors on TIL have gained importance. MATERIALS AND METHODS: In this study, stromal TIL and tertiary lymphoid structures (TLS) were determined in tumor tissues of 312 invasive and 68 in situ breast cancer patients. Expression rates of PD-1, LAG-3, and TIM-3 on intratumoral and stromal TIL were immunohistochemically evaluated. RESULTS: In invasive breast carcinomas, stromal TIL was found to be significantly associated with lymph node metastasis, HR and HER2 expression, and basal-like phenotype, as the presence of TLS with neoadjuvant therapy, recurrence, death, and expression of HR and HER2. PD-1, LAG-3, and TIM-3 expressions were found to be associated with HR and HER2 status, stromal TIL rates, and TLS. In multivariate analysis, high stromal TIL and PD-1 expression in intratumoral TIL were found to be independent prognostic factors in terms of overall survival and disease-free survival. CONCLUSION: Evaluation of TIL and immune control point receptor expressions in breast cancer is particularly important in terms of planning the therapeutic approaches based on immunotherapy protocols.

Research Burden of Interstitial Lung Diseases in Turkey - RBILD.

Introduction: The aim of our study is to investigate the etiological distribution of ILD in Turkey by stratifying the epidemiological characteristics of ILD cases, and the direct cost of initial diagnosis of the diagnosed patients. Material-Method: The study was conducted as a multicenter, prospective, cross-sectional, clinical observation study. Patients over the age of 18 and who accepted to participate to the study were included and evaluated as considered to be ILD. The findings of diagnosis, examination and treatment carried out by the centers in accordance with routine diagnostic procedures were recorded observationally. Results: In total,1070 patients were included in this study. 567 (53%) of the patients were male and 503 (47%) were female. The most frequently diagnosed disease was IPF (30.5%). Dyspnea (75.9%) was the highest incidence among the presenting symptoms. Physical examination found bibasilar inspiratory crackles in 56.2 % and radiological findings included reticular opacities and interlobular septal thickenings in 55.9 % of the cases. It was observed that clinical and radiological findings were used most frequently (74.9%) as a diagnostic tool. While the most common treatment approaches were the use of systemic steroids and antifibrotic drugs with a rate of 30.7% and 85.6%, respectively. The total median cost from the patient's admission to diagnosis was 540 Turkish Lira. Conclusion: We believe that our findings compared with data from other countries will be useful in showing the current situation of ILD in our country to discuss this problem and making plans for a solution.

Development of electrochemical aptasensors detecting phosphate ions on TMB substrate with epoxy-based mesoporous silica nanoparticles.

This study, it is aimed to develop an electrochemical aptasensor that can detect phosphate ions using 3.3'5.5' tetramethylbenzidine (TMB). It is based on the principle of converting the binding affinity of the target molecule phosphate ion (PO43-) into an electrochemical signal with specific aptamer sequences for the aptasensor to be developed. The aptamer structure served as a gate for the TMB to be released and was used to trap the TMB molecule in mesoporous silica nanoparticles (MSNPs). The samples for this study were characterized by transmission electron spectroscopy (TEM), Brunner-Emmet-Teller, dynamic light scattering&electrophoretic light scattering, and induction coupled plasma atomic emission spectroscopy. According to TEM analysis, MSNPs have a morphologically hexagonal structure and an average size of 208 nm. In this study, palladium-carbon nanoparticles (Pd/C NPs) with catalytic reaction were used as an alternative to the biologically used horseradish peroxidase (HRP) enzyme for the release of TMB in the presence of phosphate ions. The limit of detection (LOD) was calculated as 0.983 µM, the limit of determination (LOQ) was calculated as 3.276 µM, and the dynamic linear phosphate range was found to be 50-1000 µM. The most important advantage of this bio-based aptasensor assembly is that it does not contain molecules such as a protein that cannot be stored for a long time at room temperature, so its shelf life is very long compared to similar systems developed with antibodies. The proposed sensor shows good recovery in phosphate ion detection and is considered to have great potential among electrochemical sensors.

Surface microbiota and associated staphylococci of houseflies (Musca domestica) collected from different environmental sources.

Houseflies (Musca domestica) are important mechanical vectors for the transmission of pathogenic microorganisms. In this study, 129 houseflies (69 males and 60 females) were collected from 10 different environmental sources and a laboratory population was used. The surface microbiota of houseflies was identified by Next-Generation Sequencing. Staphylococci from the surfaces of houseflies were selectively isolated and their virulence genes, antibiotic susceptibilities, biofilm formation, and clonal relatedness were determined. Metagenomic analysis results demonstrated that Staphylococcus, Bacillus, and Enterococcus were mostly present on the surface of houseflies at the genus level. Additionally, the isolated 32 staphylococcal strains were identified as Staphylococcus sciuri (n = 11), S. saprophyticus (n = 9), S. arlettae (n = 6), S. xylosus (n = 4), S. epidermidis (n = 1) and S. gallinarum (n = 1). tetK, tetM, tetL, ermC, msrAB, and aad6 genes were found to carry by some of the staphylococcal strains. The strains were mostly resistant to oxacillin, penicillin, and erythromycin and three strains were multi-drug resistant. There was a statistical difference between housefly collection places and antibiotic resistance of isolated staphylococci to penicillin G, gentamicin, and erythromycin (p < 0.05). Biofilm test showed that 17 strains were strong biofilm formers, and it plays important role in the transmission of these bacteria on the surface of houseflies. Staphylococcal strains showed extracellular proteolytic and lipolytic activity in 31 and 12 strains, respectively. Closely related species were found in PFGE analysis from different environmental sources. By this study, surface microbiota and carriage of pathogenic staphylococci on the surfaces of houseflies and their virulence properties were elucidated.

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).

Binary-QSAR guided virtual screening of FDA approved drugs and compounds in clinical investigation against SARS-CoV-2 main protease.

With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (Mpro). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 Mpro.

Microbial community of soda Lake Van as obtained from direct and enriched water, sediment and fish samples.

Soda lakes are saline and alkaline ecosystems that are considered to have existed since the first geological records of the world. These lakes support the growth of ecologically and economically important microorganisms due to their unique geochemistry. Microbiota members of lakes are valuable models to study the link between community structure and abiotic parameters such as pH and salinity. Lake Van is the largest endroheic lake and in this study, bacterial diversity of lake water, sediment, and pearl mullet (inci kefali; Alburnus tarichi), an endemic species of fish which are collected from different points of the lake, are studied directly and investigated meticulously using a metabarcoding approach after pre-enrichment. Bacterial community structures were identified using Next Generation Sequencing of the 16S rRNA gene. The analysis revealed that the samples of Lake Van contain high level of bacterial diversity. Direct water samples were dominated by Proteobacteria, Cyanobacteria, and Bacteroidota, on the other hand, pre-enriched water samples were dominated by Proteobacteria and Firmicutes at phylum-level. In direct sediment samples Proteobacteria, whereas in pre-enriched sediment samples Firmicutes and Proteobacteria were determined at highest level. Pre-enriched fish samples were dominated by Proteobacteria and Firmicutes at phylum-level. In this study, microbiota members of Lake Van were identified by taxonomic analysis.

Targeted mesoporous silica nanoparticles for improved inhibition of disinfectant resistant Listeria monocytogenes and lower environmental pollution.

Benzalkonium chloride (BAC) is a common ingredient of disinfectants used for industrial, medical, food safety and domestic applications. It is a common pollutant detected in surface and wastewaters to induce adverse effects on Human health as well as aquatic and terrestrial life forms. Since disinfectant use is essential in combatting against microorganisms, the best approach to reduce ecotoxicity level is to restrict BAC use. We report here that encapsulation of BAC in mesoporous silica nanoparticles can provide an efficient strategy for inhibition of microbial activity with lower than usual concentrations of disinfectants. As a proof-of-concept, Listeria monocytogenes was evaluated for minimum inhibitory concentration (MIC) of nanomaterial encapsulated BAC. Aptamer molecular gate structures provided a specific targeting of the disinfectant to Listeria cells, leading to high BAC concentrations around bacterial cells, but significantly reduced amounts in total. This strategy allowed to inhibition of BAC resistant Listeria strains with 8 times less the usual disinfectant dose. BAC encapsulated and aptamer functionalized silica nanoparticles (AptBACNP) effectively killed only target bacteria L. monocytogenes, but not the non-target cells, Staphylococcus aureus or Escherichia coli. AptBACNP was not cytotoxic to Human cells as determined by in vitro viability assays.

Antibiotic administration in targeted nanoparticles protects the faecal microbiota of mice.

Antibiotic therapy comes with disturbances on human microbiota, resulting in changes of bacterial communities and thus leading to well-established health problems. In this study, we demonstrated that targeted teicoplanin administration maintains the faecal microbiota composition undisturbed in a mouse model while reaching therapeutic improvements for S. aureus infection.

PD-L1 expression in immune cells is a favorable prognostic factor for nasopharyngeal carcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) has been determined as a reliable prognostic factor for various malignancies. In this study, we aimed to determine the prognostic effect of PD-L1 expression in tumor-infiltrating immune cells (TIICs) of nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy patients diagnosed with non-metastatic NPC were included in the study. PD-L1 expression on immune cells was analyzed by immunohistochemical method. Patients were categorized into two groups according to the PD-L1 expression level in TIICs (level of PD-L1 staining ≥5% positive vs <5% negative). RESULTS: Median follow-up period was 34 months (range = 1 - 188). 1 and 2 years survival rate were found as 75% and 63% in PD-L1 negative TIICs group (47%), and 85% and 83% in PD-L1 positive TIICs group (53%), respectively. PD-L1 positivity in immune cells (ICs) was detected in 53% of the patients. The survival rate was found better in the PD- L1 positive group compared to the negative group (P = 0.049). DISCUSSION: In conclusion, the survival rate was found significantly better in the PD-L1 positive TIICs group, compared to the negative group.

Good prognostic factor in patients with nonmetastatic nasopharyngeal carcinoma: Programmed death ligand-1 expression in tumor cells.

PURPOSE: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. PATIENTS AND METHODS: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. RESULTS: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). CONCLUSION: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.