Anatomical Trajectory of the Corrugator Supercilii Muscle in Koreans: Implications for Aesthetic and Clinical Practices.

BACKGROUND: Understanding the attachment patterns of the corrugator supercilii muscle (CS) is vital for treatments designed to improve facial symmetry and functionality. OBJECTIVES: The aim of this research was to elucidate the anatomical trajectory and intricate relationships of the CS within the upper face and midface, specifically focusing on its connections with the frontalis (FT) and orbicularis oculi (OOc) muscles. METHODS: The CS was examined in 41 specimens of embalmed adult Korean cadavers using microdissection, histological analyses, and microcomputed tomography, an in-depth exploration of its anatomical positioning and intricate interactions with adjacent muscles. RESULTS: Some lower fibers of the CS extended to the upper orbital part of the OOc in 59.5% of cases, while the CS interdigitated or blended exclusively with the FT in 40.5% of cases. The fibers of the CS demonstrated diverse extensions towards the upper face and midface, exhibiting varied trajectories and lengths. Additionally, lower fibers of the CS extended to significant anatomical landmarks such as the OOc, malaris muscle, and the superficial musculoaponeurotic system (SMAS). CONCLUSIONS: This study demonstrates that precise understanding of the CS and its relationship with the FT and OOc is crucial for optimizing invasive or non-invasive treatment like botulinum toxin injection, SMAS lifting and browplasty surgery. The extension of lower fibers of the CS to significant anatomical landmarks indicates complex interactions with adjacent facial structures, highlighting the necessity of detailed anatomical knowledge for clinical applications.

Molecular detection of lacrimal apparatus and ocular surface - related ABC transporter genes.

The ocular system is in constant interaction with the environment and with numerous pathogens. The ATP-binding cassette (ABC) transporters represent one of the largest groups among the transmembrane proteins. Their relevance has been demonstrated for their defense function against biotic and abiotic stress factors, for metabolic processes in tumors and for their importance in the development of resistance to drugs. The aim of this study was to analyze which ABC transporters are expressed at the ocular surface and in the human lacrimal apparatus. Using RT-PCR, all ABC transporters known to date in humans were examined in tissue samples from human cornea, conjunctiva, meibomian glands and lacrimal glands. The RT-PCR analyses revealed the presence of all ABC transporters in the samples examined, although the results for some of the 48 transporters known in human and analyzed were different in the various tissues. The present results provide information on the expression of ABC transporters at the mRNA level on the ocular surface and in the lacrimal system. Their detection forms the basis for follow-up studies at the protein level, which will provide more information about their physiological significance at the ocular surface and in the lacrimal system and which may explain pathological effects such as drug resistance.

Feasibility of 3 Tesla MRI for the assessment of mid-palatal suture maturation: a retrospective pilot study.

The maxilla occupies a key position in dentofacial orthopaedics, since its transversal development can be directly influenced by orthodontic therapy. The maturation stages of the mid-palatal suture, which are obtained from cone-beam computed tomography images (CBCT), present an addition to clinical decision-making in transversal discrepancies of the upper jaw. In an endeavour to reduce ionizing radiation in adolescents and young adults, who are particularly susceptible to long term stochastic irradiation effects, we investigated the feasibility of 3 Tesla (3T) MRI in detecting the maturation stages of the mid-palatal suture. A collective of 30 patients aged 24-93 years with routine neck MRI at 3T, underwent an additional three-dimensional isotropic T1 weighted study sequence of the midface. Image evaluation was performed on axial, multi-planar formatted reconstructions of the dataset aligned to the midline axis of the palate, and curved reconstructions aligned to the concavity of the palate. Inverted images helped to achieve an image impression similar to the well-known CBCT appearance. All datasets were reviewed by three readers and mid-palatal maturation was scored twice according to Angelieri et al. Intra- and inter-rater agreement were evaluated to measure the robustness of the images for clinical evaluation. 3T MRI deemed reliable for the assessment of mid-palatal suture maturation and hence for the appraisal of the hard palate and its adjacent sutures. The data of this pilot study display the feasibility of non-ionizing cross-sectional MRI for the determination of sutural maturation stages. These findings underline the potential of MRI for orthodontic treatment planning, further contributing to the avoidance of unnecessary radiation doses.

A vascularized in vivo melanoma model suitable for metastasis research of different tumor stages using fundamentally different bioinks.

Although 2D cancer models have been the standard for drug development, they don't resemble in vivo properties adequately. 3D models can potentially overcome this. Bioprinting is a promising technique for more refined models to investigate central processes in tumor development such as proliferation, dormancy or metastasis. We aimed to analyze bioinks, which could mimic these different tumor stages in a cast vascularized arteriovenous loop melanoma model in vivo. It has the advantage to be a closed system with a defined microenvironment, supplied only with one vessel-ideal for metastasis research. Tested bioinks showed significant differences in composition, printability, stiffness and microscopic pore structure, which led to different tumor stages (Matrigel and Alg/HA/Gel for progression, Cellink Bioink for dormancy) and resulted in different primary tumor growth (Matrigel significantly higher than Cellink Bioink). Light-sheet fluorescence microscopy revealed differences in vascularization and hemorrhages with no additional vessels found in Cellink Bioink. Histologically, typical human melanoma with different stages was demonstrated. HMB-45-positive tumors in progression inks were infiltrated by macrophages (CD163), highly proliferative (Ki67) and metastatic (MITF/BRN2, ATX, MMP3). Stainings of lymph nodes revealed metastases even without significant primary tumor growth in Cellink Bioink. This model can be used to study tumor pathology and metastasis of different tumor stages and therapies.

Effect of micro- and nanoplastic particles on human macrophages.

Micro- and nanoplastics (MNPs) are ubiquitous in the environment, resulting in the uptake of MNPs by a variety of organisms, including humans, leading to particle-cell interaction. Human macrophages derived from THP-1 cell lines take up Polystyrene (PS), a widespread plastic. The question therefore arises whether primary human macrophages also take up PS micro- and nanobeads (MNBs) and how they react to this stimulation. Major aim of this study is to visualize this uptake and to validate the isolation of macrophages from peripheral blood mononuclear cells (PBMCs) to assess the impact of MNPs on human macrophages. Uptake of macrophages from THP-1 cell lines and PBMCs was examined by transmission electron microscopy (TEM), scanning electron microscopy and live cell imaging. In addition, the reaction of the macrophages was analyzed in terms of metabolic activity, cytotoxicity, production of reactive oxygen species (ROS) and macrophage polarization. This study is the first to visualize PS MNBs in primary human cells using TEM and live cell imaging. Metabolic activity was size- and concentration-dependent, necrosis and ROS were increased. The methods demonstrated in this study outline an approach to assess the influence of MNP exposure on human macrophages and help investigating the consequences of worldwide plastic pollution.

Shaping Efficiency of Rotary and Reciprocating Kinematics of Engine-driven Nickel-Titanium Instruments in Moderate and Severely curved Root Canals Using Microcomputed Tomography: A Systematic Review of Ex Vivo Studies.

INTRODUCTION: This systematic review aimed to compare reciprocating with continuous rotary instrumentation kinematics, by means of microcomputed tomography evaluations, in extracted human permanent teeth with moderate and severe canal curvatures. METHODS: The research protocol was registered in the International Prospective Register of Systematic Reviews and given the reference number CRD42023404035. An electronic search was undertaken in MEDLINE (PubMed), EBSCO, Scopus, Web of Science databases until December 2021. Manual screening of issues in endodontic journals and references of relevant articles were assessed individually. The risk of bias (RoB) of the included articles was evaluated with the QUIN tool (Quality Assessment Tool for In Vitro Studies). RESULTS: Among 1640 retrieved articles, 49 were included in the qualitative synthesis. Fifteen articles had low RoB, 33 articles had medium RoB, and only 1 study was at high RoB. Continuous rotary systems had better centering ability in both moderate and severe canal curvatures and resulted in less apical transportation in severely curved root canals. None of the kinematic systems was capable of instrumenting the entire canal surface area. Reciprocating kinematics systems tended to provide higher increase in surface area of severely curved canals and produced fewer dentinal microcracks in moderately curved canals. CONCLUSIONS: The evidence presented in this review suggests that continuous rotary system seems to be better than reciprocating system in solving the major issues encountered during root canal instrumentation of extracted teeth with moderate and severe curvatures.

Historical Profiling of Dry Eye Patients - Potential Trigger Factors and Comorbidities.

PURPOSE: Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. MATERIALS AND METHODS: In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18 - 87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). RESULTS: DES occurred with significantly (p < 0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidaemia, hyperuricaemia, osteoporosis, and nephrolithiasis. CONCLUSION: Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.

Dacryolithogenesis or Dacryolithiasis-The Story So Far.

The term dacryoliths refers to the concretions found within the lacrimal system. When the term dacryoliths is unspecified, it usually refers to the noninfectious dacryoliths commonly isolated from the lacrimal sac and the nasolacrimal duct. More often, they are diagnosed incidentally during a dacryocystorhinostomy, and the reported incidence among all dacryocystorhinostomy surgeries is 5.7% to as high as 18%. Dacryolithiasis is a complex process occurring within the lacrimal system, and current evidence suggests a multifactorial etiology. The sequence of events can be summarized broadly into 4 stages: stage of susceptibility, stage of initiation/trigger, stage of development, and stage of maintenance. The triggering event is the breach of the lacrimal sac or nasolacrimal duct epithelium, resulting in microtrauma with blood leakage. The blood clots act as a nidus for subsequent sequential laying of mucopeptides, cellular debris present locally, debris washed from the ocular surface, and extraneous agents in tears. This process is aided by altered rheology and composition of the tear film. After the formation of dacryoliths, extracellular neutrophil traps usually form on the surface, which help to maintain the dacryoliths (which do not dissolve). This review highlights and discusses the possible sequence of events during dacryolithiasis.

New Insights Into the Anatomy of the Eyelashes With Regard to Ethnic Differences Against a Clinical Background.

BACKGROUND: To investigate the root depth, root angle, and light and scanning electron microscopical anatomy of human eyelashes relevant to eyelash ablation. METHODS: Eyelash root depth, the angle between eyelash root and skin epithelium, spatial relationship, and scanning electron microscopical features of the eyelashes were studied on 4 upper and 4 lower eyelids of Caucasian (n = 4) and Indian (n = 4) cadaver heads according to a set protocol. RESULTS: There were significant differences in the mean eyelash root depth between Indians (2.3 ± 0.38 mm) and Caucasians (1.9 ± 0.26 mm; p = 0.007), as well as between upper eyelids and lower eyelids (1.9 ± 0.2 mm vs. 1.8 ± 0.1 mm). The mean angle between the lash follicle root and the skin epithelium was 75 ± 11 degrees and similar in both ethnic groups. The eyelash bulb was located close to the tarsal plate and meibomian glands and formed an angle of less than 15 degrees with the eyelash root. Scanning electron microscopy studies revealed that the eyelash bulb was 202 ± 12 µm wide in Indians and 170.6 ± 16.8 µm wide in Caucasian eyelids ( p = 0.08). The eyelashes were placed more closely in Indian eyelids than in Caucasian eyelids ( p = 0.03). The width of the cuticle layer varied between the hair shaft and the inner eyelid segment. CONCLUSIONS: There are differences in eyelash root depth, inter-eyelash distance, and cuticle thickness between Indian and Caucasian eyelids. The oblique orientation of the eyelash root and close proximity of the eyelash bulb to the tarsal plate should be kept in mind while doing the electroepilation procedure.

Transcutaneous (External) Dacryocystorhinostomy with Reconstruction of the Ductus nasolacrimalis. / Transkutane (externe) Dakryozystorhinostomie mit Rekonstruktion des Ductus nasolacrimalis.

BACKGROUND: Dacryocystorhinostomy (DCR) is regarded as the gold standard for the treatment of chronic dacryocystitis (CDC). Different modifications of the surgical procedure have been developed over the years. METHODS: Patients with CDC due to postsaccal lacrimal stenosis and under treatment with DCR have been included in this retrospective study. Two groups of different surgical procedures were analysed: firstly DCR without reconstruction of the ductus nasolacrimalis (DNL, group 1) and secondly patients with reopening the DNL (group 2). Criteria for success were absence of permanent epiphora, absence of inflammation of the lacrimal sac (functional success), and no recurrent surgery with free patency of the lacrimal duct (anatomical success). This was obtained by questionnaire after a follow-up of at least 12 months. The impact of gender, ectasia of the lacrimal sac, dacryoliths, and prior lacrimal surgeries was analysed. RESULTS: Overall, 248 surgeries were enrolled in this trial. Mean age in group 1 was 68 years (range: 22 to 92 years) and gender ratio was 3.2 to 1 (female : male). In that group, 68 operations could be followed up. In group 2, 62 operations on patients of a mean age of 63 years (range: 24 to 89 years) and a gender ratio of 2.9 to 1 (female : male) were observed. Complete success occurred in 75.0% in group 1 and 75.8% in group 2. Recurrent operations were necessary in one case of group 2 (1.6%) and 4 cases of group 1 (5.9%). Gender (group 1 p = 1; group 2 p = 0.115; between groups p = 0.511), ectasia of the lacrimal sac (group 1 p = 0.877; group 2 p = 0.674; between groups p = 0.878), dacryolith (group 1 p = 1; group 2 p = 0.465; between groups p = 1), and prior lacrimal surgery (group 1 p = 0.092; group 2 p = 0.051; between groups p = 0.520) did not influence the success rates in each group or between groups. Significantly more dacryoliths were found during operations of group 2 (p = 0.010). CONCLUSION: Reconstruction of the DNL during DCR is a possible and easy modification, with a slightly better success rate in curing CDC. Intraoperatively, dacryoliths might not be apparent remain in the deeper parts of the lacrimal ducts. Therefore, these segments should be inspected during surgery.

Suitability of Slaughterhouse-Acquired Pig Eyes as Model Systems for Refractive Ultraviolet and Infrared Femtosecond Laser Research.

PURPOSE: To elucidate whether it is feasible to use porcine eyes from scalded, abattoir-acquired animals for refractive femtosecond laser research. METHODS: An infrared laser (FS 200) and an ultraviolet laser (prototype version) were tested for their applicability on scalded pig eyes. Fifty porcine eyes were divided into two equally-sized groups and assigned to either the infrared or the ultraviolet laser. Both laser groups were comprised of five subgroups of n = 5 eyes each. Group A: non-scalded eyes (negative control); group B: eyes taken from tunnel-scalded animals; group C1: eyes taken from tank-scalded animals without opaque corneal lesion; group C2: eyes taken from animals with opaque corneal lesion; group D: eyes scalded in toto in the laboratory (positive control). In each group the lasers were employed to create a stromal flap. The quality of the laser cuts and the resulting flap beds, as well as of the porcine corneas themselves, was examined by anterior segment optical coherence tomography and scanning electron microscopy. RESULTS: All scalded specimens exhibited substantial corneal swelling, most pronounced in group C2. After ultraviolet laser application, the tank- and tunnel-scalded samples displayed marked irregularities and an increased degree of surface roughness in the flap beds. After infrared laser application, this was only the case in the tank-scalded specimens. CONCLUSION: It is not recommended to use eyes taken from scalded pigs for ultraviolet femtosecond laser experiments. For infrared femtosecond lasers, eyes taken from tunnel-scalded animals may represent an acceptable alternative, if non-scalded eyes are not available.

The accessory heads of the quadriceps femoris muscle may affect the layering of the quadriceps tendon and potential graft harvest lengths.

PURPOSE: The aim of the study was to assess the quadriceps femoris system for the presence of additional layers. METHODS: One hundred and twenty-eight lower limbs fixed in 10% formalin were examined. RESULTS: Five types of quadriceps tendon layering were found based on the accessory heads of the quadriceps muscle. Type I (55%)-represented by four heads and four layers, and it was something new because standard orthopaedic textbooks described quadriceps tendon as a structure composed of only three layers. Type II (27.4%)-the first four layers were the same as in Type 1, but the accessory tendon of the fifth head of the quadriceps femoris muscle had the deepest attachments. Type III (10.9%)-this type included 6 heads of quadriceps femoris. It consisted of five layers. Type IV (3.1%)-this type included 7 quadriceps femoris heads. This type consisted of only four layers. Type V (3.1%)-this type included 8 heads of the quadriceps femoris heads. This type consist of 5 layers. CONCLUSION: The findings of this study provide a detailed anatomy of the quadriceps tendon including the accessory tendons of the accessory heads of the quadriceps tendon. The accessory heads of the quadriceps femoris muscle contribute to the layering of the quadriceps tendon. The second conclusion of this study is the development of safe distances depending on the types. Not all types are perfect for harvesting-Type IV seems to be the safest type, in turn Type V the most dangerous.

Introducing the Foveola lunata, an anatomical landmark of the wrist.

The lunate foveola is often the starting point of a cystic swelling called a "ganglion". To make the anatomy of this region more relevant to the needs of clinicians and more accessible to students, we propose to introduce the term lunate foveola (Foveola lunata) on the dorsal side of the wrist just distal to the os lunatum. The easily located foveola will help in the examination of the wrist to more easily understand the anatomy of the wrist and facilitate the examination of patients with wrist injuries when an injury to the lunate (Os lunatum) is suspected.

Inverse identification of region-specific hyperelastic material parameters for human brain tissue.

The identification of material parameters accurately describing the region-dependent mechanical behavior of human brain tissue is crucial for computational models used to assist, e.g., the development of safety equipment like helmets or the planning and execution of brain surgery. While the division of the human brain into different anatomical regions is well established, knowledge about regions with distinct mechanical properties remains limited. Here, we establish an inverse parameter identification scheme using a hyperelastic Ogden model and experimental data from multi-modal testing of tissue from 19 anatomical human brain regions to identify mechanically distinct regions and provide the corresponding material parameters. We assign the 19 anatomical regions to nine governing regions based on similar parameters and microstructures. Statistical analyses confirm differences between the regions and indicate that at least the corpus callosum and the corona radiata should be assigned different material parameters in computational models of the human brain. We provide a total of four parameter sets based on the two initial Poisson's ratios of 0.45 and 0.49 as well as the pre- and unconditioned experimental responses, respectively. Our results highlight the close interrelation between the Poisson's ratio and the remaining model parameters. The identified parameters will contribute to more precise computational models enabling spatially resolved predictions of the stress and strain states in human brains under complex mechanical loading conditions.

Epithelial-mesenchymal transition in the lacrimal gland morphogenesis, damage and repair.

Epithelial-mesenchymal transition (EMT) constitutes an important pathway in organ fibrosis seen in the lungs, liver, eye, and salivary glands. This review summarizes the EMT observed within the lacrimal gland during its development, tissue damage and repair along with possible translational implications. Existing animal and human studies have reported the increased expression of EMT regulators i.e., transcription factors like Snail, TGF-ß1 within the lacrimal glands, and a possible role of reactive oxygen species, which might be initiating the cascade of EMT. In these studies, EMT is typically detected by reduced E-cadherin expression in the epithelial cells and increased Vimentin and Snail expression within the lacrimal glands' myoepithelial or ductal epithelial cells. Other than specific markers, electron microscopic evidence of disrupted basal lamina, increased collagen deposition, reorganised cytoskeleton of myoepithelial cells also indicated EMT. Very few studies have shown myoepithelial cells to be the cells transitioning into mesenchymal cells with increased extracellular matrix deposition within the lacrimal glands. EMT in animal models seemed reversible as glands got repaired after damage with IL-1α injection or duct ligation and transiently used the EMT as a means for tissue repair. The EMT cells also expressed nestin, a marker for progenitor cells in a rabbit duct ligation model. However, lacrimal glands of ocular graft versus host disease and IgG4 dacryoadenitis demonstrate irreversible acinar atrophy along with signs of EMT-fibrosis, reduced E-cadherin, and increased Vimentin and Snail expression. Future studies exploring the molecular mechanisms of EMT and thereby developing targeted therapies capable of transforming the mesenchymal cells into epithelial cells or blocking the EMT might help in the restoration of the lacrimal gland function.

C1q/TNF-Related Proteins 1, 6 and 8 Are Involved in Corneal Epithelial Wound Closure by Targeting Relaxin Receptor RXFP1 In Vitro.

Inadequate wound healing of ocular surface injuries can lead to permanent visual impairment. The relaxin ligand-receptor system has been demonstrated to promote corneal wound healing through increased cell migration and modulation of extracellular matrix formation. Recently, C1q/tumor necrosis factor-related protein (CTRP) 8 was identified as a novel interaction partner of relaxin receptor RXFP1. Additional data also suggest a role for CTRP1 and CTRP6 in RXFP1-mediated cAMP signaling. However, the role of CTRP1, CTRP6 and CTRP8 at the ocular surface remains unclear. In this study, we investigated the effects of CTRP1, CTRP6, and CTRP8 on epithelial ocular surface wound closure and their dependence on the RXFP1 receptor pathway. CTRP1, CTRP6, and CTRP8 expression was analyzed by RT-PCR and immunohistochemistry in human tissues and cell lines derived from the ocular surface and lacrimal apparatus. In vitro ocular surface wound modeling was performed using scratch assays. We analyzed the effects of recombinant CTRP1, CTRP6, and CTRP8 on cell proliferation and migration in human corneal and conjunctival epithelial cell lines. Dependence on RXFP1 signaling was established by inhibiting ligand binding to RXFP1 using a specific anti-RXFP1 antibody. We detected the expression of CTRP1, CTRP6, and CTRP8 in human tissue samples of the cornea, conjunctiva, meibomian gland, efferent tear ducts, and lacrimal gland, as well as in human corneal, conjunctival, and meibomian gland epithelial cell lines. Scratch assays revealed a dose-dependent increase in the closure rate of surface defects in human corneal epithelial cells after treatment with CTRP1, CTRP6, and CTRP8, but not in conjunctival epithelial cells. Inhibition of RXFP1 fully attenuated the effect of CTRP8 on the closure rate of surface defects in human corneal epithelial cells, whereas the CTRP1 and CTRP6 effects were not completely suppressed. Conclusions: Our findings demonstrate a novel role for CTRP1, CTRP6, and CTRP8 in corneal epithelial wound closure and suggest an involvement of the relaxin receptor RXFP1 signaling pathway. This could be a first step toward new approaches for pharmacological and therapeutic intervention.

Acute colonic flexures: the basis for developing an artificial intelligence-based tool for predicting the course of colonoscopy.

Tortuosity of the colon is an important parameter for predicting the course of colonoscopy. Computed tomography scans of the abdominal cavity were performed in 224 (94 female, 130 male) adult subjects. The number of acute (angle not exceeding 90°) bends between adjacent colonic segments was noted and analyzed. Data were analyzed for correlation with gender, age, height and weight. An artificial intelligence algorithm was proposed to predict the course of colonoscopy. We determined the number of acute flexions in females to be 9.74 ± 2.5 (min-max: 4-15) and in males to be 8.7 ± 2.75 (min-max: 4-20). In addition, more acute flexions were found in women than in men and in older women (after 60 years) and men (after 80 years) than in younger ones. We found the greatest variability in the number of acute flexures in the sigmoid colon (0-9), but no correlation was found between the number of acute flexures and age, gender, height or BMI. In the transverse colon, older and female subjects had more flexures than younger and male subjects, respectively. Older subjects had more acute flexures in the descending colon than younger subjects. There are opportunities to use the number of acute flexures (4-7, 8-12, more than 12 flexures) to classify patients into appropriate risk categories for future incomplete colonoscopy. On this basis, we predicted troublesome colonoscopies in 14.9% female and in 6.1% male subjects.

Anti-inflammatory effects of an autologous gold-based serum therapy in osteoarthritis patients.

Osteoarthritis (OA) involves activation and recruitment of immune cells to affected joints, including the production of pro-inflammatory cytokines. Here, a gold-based autologous serum therapy is investigated for its effect on peripheral blood cell composition and cytokine levels in OA patients. From six OA patients serum and blood samples were collected before and after second therapy treatment for analysis of peripheral blood cell composition as well as cytokine levels compared to control samples. This therapy significantly downregulates CD4+ T cells and B cells in OA patients after second treatment compared to healthy controls. Monocytes are significantly upregulated in patients after second treatment Serum IL-9 and TNF-α levels are downregulated in patients after second treatment compared to healthy control serum. The activation status of immune cells was modulated after therapy in patients. Anti-inflammatory effects of the peripheral blood cell composition in OA patients can be seen after therapy treatment. After two treatments IL-9 and TNF-α are significantly downregulated in patient serum. Here, primary data of a new autologous therapy for OA treatment and its modulatory effects on cytokines are presented.

MyoBio: An Automated Bioreactor System Technology for Standardized Perfusion-Decellularization of Whole Skeletal Muscle.

OBJECTIVE: Decellularizing solid organs is a promising top-down process to produce acellular bio-scaffolds for 'de novo' regrowth or application as tissue 'patches' that compensate, e.g., large volumetric muscle loss in reconstructive surgery. Therefore, generating standardized acellular muscle scaffolds marks a pressing area of need. Although animal muscle decellularization protocols were established, those are mostly manually performed and lack defined bioreactor environments and metrologies to assess decellularization quality in real-time. To close this gap, we engineered an automated bioreactor system to provide chemical decellularization solutions to immersed whole rat gastrocnemius medialis muscle through perfusion of the main feeding arteries. RESULTS: Perfusion control is adjustable according to decellularization quality feedback. This was assessed both from (i) ex situ assessment of sarcomeres/nuclei through multiphoton fluorescence and label-free Second Harmonic Generation microscopy and DNA quantification, along with (ii) in situ within the bioreactor environment assessment of the sample's passive mechanical elasticity. CONCLUSION: We find DNA and sarcomere-free constructs after 72 h of 0.1% SDS perfusion-decellularization. Furthermore, passive elasticity can be implemented as additional online decellularization quality measure, noting a threefold elasticity decrease in acellular constructs. SIGNIFICANCE: Our MyoBio represents a novel and useful automated bioreactor environment for standardized and controlled generation of acellular whole muscle scaffolds as a valuable source for regenerative medicine.

TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?

The study of transient receptor potential (TRP) channels has dramatically increased during the past few years. TRP channels function as sensors and effectors in the cellular adaptation to environmental changes. Here, we review literature investigating the physiological and pathophysiological roles of TRPC channels in the renal tubular system with a focus on TRPC3 and TRPC6. TRPC3 plays a key role in Ca2+ homeostasis and is involved in transcellular Ca2+ reabsorption in the proximal tubule and the collecting duct. TRPC3 also conveys the osmosensitivity of principal cells of the collecting duct and is implicated in vasopressin-induced membrane translocation of AQP-2. Autosomal dominant polycystic kidney disease (ADPKD) can often be attributed to mutations of the PKD2 gene. TRPC3 is supposed to have a detrimental role in ADPKD-like conditions. The tubule-specific physiological functions of TRPC6 have not yet been entirely elucidated. Its pathophysiological role in ischemia-reperfusion injuries is a subject of debate. However, TRPC6 seems to be involved in tumorigenesis of renal cell carcinoma. In summary, TRPC channels are relevant in multiples conditions of the renal tubular system. There is a need to further elucidate their pathophysiology to better understand certain renal disorders and ultimately create new therapeutic targets to improve patient care.