Degenerative Changes Research Articles

Unveiling the Gut-Disc Axis: How Microbiome Dysbiosis Accelerates Intervertebral Disc Degeneration.

The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.

Evaluation of the Safety and Efficacy of Curcumin-Synthesized Silver Nanoparticles in Rats Exposed to Chlorpyrifos During Puberty Development.

Silver nanoparticles (Ag-NPs) have garnered significant attention in recent years due to their therapeutic effects. Curcumin (CUR) has been utilized as a coating agent for synthesizing Ag-NPs, intended to act as a potential drug. This study was designed to evaluate the safety and efficacy of curcuminsynthesized silver nanoparticles on rats exposed to chlorpyrifos (CPF) during their pubertal development. Forty-two male Wistar rats, 23 days old, were selected and randomly divided into 7 groups (n=6) as follows: positive control, negative control, CPF (5 mg/kg), silver nanoparticles synthesized using curcumin at 40 μg/kg (CUR-Ag-NPs 40), CUR-Ag-NPs 80, CPF+ CUR-Ag-NPs 40, CPF+ CUR-AgNPs 80. All treatments were administered via gavage for 30 days. At the end of the study, rats were anesthetized using ketamine (50 mg/kg), and xylazine, (10 mg/kg) and blood was collected from the heart for serum analysis of liver enzymes, urea, and creatinine. Liver and kidney tissues were isolated for histopathological analysis. No significant differences were observed in serum levels of AST, ALT, and ALP enzymes as well as urea and creatinine levels among the different groups. Light microscopy observation revealed multifocal inflammatory mononuclear cell subsets in liver tissue associated with mild inflammatory mononuclear cell infiltration in the portal region in CPF, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40, and CPF+CUR-Ag- NPs 80 groups. Histological examination of kidney tissue showed degenerative changes in the tubular epithelium, congestion, and mild infiltration of mononuclear inflammatory cells in the renal interstitial tissue in the CPF group, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40 and CPF+CUR-Ag-NPs 80 groups. This study failed to establish the safety and efficacy of CUR-Ag-NP at 40 and 80 μg/kg in prepubertal rats exposed to CPF. However, further studies should be conducted to thoroughly characterize the efficacy of CUR-Ag-NP in developmental animal models.

Various Strategies of Tendon Stem/Progenitor Cell Reprogramming for Tendon Regeneration.

Rotator cuff tears (RCT) are the most common cause of shoulder pain among adults. "Rotator cuff" refers to the four muscles that cover the shoulder joint: supraspinatus, infraspinatus, subscapularis, and teres minor. These muscles help maintain the rotational movement and stability of the shoulder joint. RCT is a condition in which one or more of these four muscles become ruptured or damaged, causing pain in the arms and shoulders. RCT results from degenerative changes caused by chronic inflammation of the tendons and consequent tendon tissue defects. This phenomenon occurs because of the exhaustion of endogenous tendon stem cells. Tendon regeneration requires rejuvenation of these endogenous tendon stem/progenitor cells (TSPCs) prior to their growth phase. TSPCs exhibit clonogenicity, multipotency, and self-renewal properties; they express classical stem cell markers and genes associated with the tendon lineage. However, specific markers for TSPC are yet to be identified. In this review, we introduce novel TSPC markers and discuss various strategies for TSPC reprogramming. With further research, TSPC reprogramming technology could be adapted to treat age-related degenerative diseases, providing a new strategy for regenerative medicine.

Cervical Myeloradiculopathy With Bilateral Foraminal Stenosis Treated by Unilateral Biportal Endoscopic Decompression with Alternating Hemilaminectomy and Bilateral foraminotomy: A Case Report and Technical Note

Cervical myeloradiculopathy is a debilitating condition characterized by progressive spinal cord dysfunction commonly caused by degenerative changes in the cervical spine. It typically exhibits an insidious onset and progressive functional decline, along with multiple exiting nerve root entrapments bilaterally in some patients. Traditional surgical interventions, such as discectomy and fusion, are associated with some complications and limitations. Unilateral biportal endoscopic (UBE) decompression can have significant advantages over traditional techniques when cervical central and bilateral foraminal decompression is required. In this case report and technical note, we describe our experience with this novel surgical technique for the treatment of cervical myelopathy. A 67-year-old patient presented with progressive neck pain; bilateral upper extremity radiculopathy; loss of power and sensation in the C5, C6, and C7 nerve root distribution; gait imbalance, and spasticity. Magnetic resonance imaging revealed multilevel cervical spondylosis with central canal and bilateral foraminal stenosis. The patient underwent UBE central and bilateral foraminal decompression. At a 9-month follow-up visit, he was able to walk unassisted, his reflexes had returned to normal, no spasticity was observed, and he had good grip strength in both hands. This is a novel technique of UBE decompression with bilateral foraminotomy at the C4–5, C5–6, and C6–7 levels and laminectomy named “the floating tip technique.” The procedure involved bilateral 3-level lamino-foraminotomy and hemilaminotomy on both C5 and C6. A hemilamina was removed on the opposite sides, and flavectomy was performed. Postoperative computed tomography findings showed an intact, complete muscular mass with an intact central spinous process. Therefore, this method was labelled the “floating tip technique.”

Investigation of The Effects of Boric Acid on Kidney Tissues in Rat with Experimental Knee Osteoarthritis

Osteoarthritis (OA) is a disease that often occurs in the knee joints and is characterized by disruption of cartilage homeostasis. Due to the systemic inflammation it creates, it affects not only the joint area, but also many tissues and organs. In this study, the damage caused by systemic inflammatory reactions due to OA in kidney tissue and the protective effect of boric acid were investigated. Wistar albino rats were used in the study. An experimental knee OA model was created by intraarticular injection of monosodium iodoacetate (MIA) in rats. To work; It was formed from 4 groups as Control, OA, OA + 4 mg Boric Acid, OA + 10 mg Boric Acid. At the end of the study, kidney tissues were taken from the rats and TNF-α, IL-1β, NOS and MMP analyzes were performed by histopathological and immunohistochemical methods. Histopathological examinations revealed severe degenerative and necrotic changes in tubular epithelial cells in the OA groups, and these changes decreased in the boric acid-administered group depending on the dose. In immunohistochemical analyzes, it was determined that systemic inflammatory reactions occurring in OA application decreased in a dose-dependent manner with boric acid application. In conclusion; It was determined that kidney tissues were damaged due to systemic inflammatory reactions in rats with OA and boric acid had a protective effect against this damage.

Cerebellar Structural and N-Acetylaspartate, Choline, and Creatine Metabolic Profiles in Parkinson's Disease and Essential Tremor.

The role of the cerebellum in Parkinson's disease (PD), particularly in tremor-dominant subtypes, is increasingly recognized. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) provide anatomical and metabolic insights, suggesting compensatory hyperactivity or degenerative changes in the cerebellum in PD. Volumetric analysis of cerebellar structures in MRI images, combined with metabolic profiles from MRS, offers possibilities for differentiating PD from essential tremor (ET). The cerebellum may be a potential therapeutic target due to its role in neurocircuitry of PD and ET. Brain structural data were obtained using MRI, and cerebellar metabolic profiles, focusing on the quantification of N-acetylaspartate (NAA), choline, and creatine peaks were obtained using MRS. This study enrolled patients with ET and PD, both with and without tremor, as well as disease controls with cerebellar atrophy (including spinocerebellar ataxia and multiple system atrophy). Volumetric analysis of cerebellar structures was performed. Differences in MRI and MRS parameters were analyzed using one-way analysis of covariance with a significance threshold of p < 0.05. From November 2018 to March 2023, 111 patients were enrolled, including 29 ET, 29 cerebellar atrophy, 12 PD without tremor, and 41 PD with tremor. No significant differences in cerebellar volume and N-acetylaspartate/creatine and choline/creatine ratios were found between ET and PD with tremor. This preliminary retrospective study suggests similarities in cerebellar structures and metabolic profiles between ET and PD, highlighting the need for advanced imaging techniques to better differentiate between these conditions. Future research should integrate clinical data, such as tremor severity and cognitive assessments, to explore the relationships with cerebellar MRI parameters.

Ancient Schwannoma in Proximity to the Median Nerve in the Midarm of an Elderly Woman

ABSTRACT Ancient schwannomas (ASs) are a rare type of schwannomas which arise from the Schwann cells. They are characterized by benign nature and long-standing course. Their histopathological hallmark is hemorrhagic and degenerative changes with nuclear atypia. They can be misdiagnosed as malignant tumors but are differentiated by absence of mitotic activity. The median nerve in the arm is rarely involved. Even rarer is the appearance of ASs away from the main median nerve. We describe a case of AS present in proximity to the median nerve in the midarm of an elderly woman. The tumor grew relatively faster over 1.5 years and the patient presented with pain and swelling in the medial side of the right midarm. Following imaging and histopathological examination (HPE), definitive diagnosis was reached. Surgical excision was done performed and further HPE confirmed AS. The patient was further subjected to external beam radiotherapy (RT; 50 Gy over 5 weeks in 25 fractions) to prevent recurrence. RT was well tolerated, and at 2 months of follow-up, there was absence of any radiological sign of recurrence. The differential diagnoses of AS include sarcomas and tumors of neural origin. History, clinical presentation, imaging, and histopathology findings are critical in arriving at the diagnosis of AS.

Unraveling Marfan hearts: ultrastructural evidence for myocardial remodeling and cardiomyopathy

Abstract Background Despite improved life expectancy for patients with Marfan syndrome (MFS), significant morbidity and mortality persist. Although primarily attributed to aortic dissection and rupture, recent studies highlight the emerging role of arrhythmias and heart failure as additional contributors to morbidity and mortality in MFS. While severe valvular heart disease is an established cause of heart failure, there is a growing recognition of primary cardiomyopathy in patients with MFS. The mechanisms underlying cardiomyopathy in MFS remain poorly understood. Purpose This study aimed to reveal insights into the ultrastructural myocardial architecture in patients with MFS, thereby elucidating the role of cardiomyopathy in MFS. Methods This study enrolled 44 patients who underwent cardiac surgery at 2 centers (Marfan syndrome patients n=27 (MFS), ascending thoracic aortic aneurysm repair patients n=5 (non-MFS), patients post-orthotopic heart transplant n=12 (controls)). Myocardial biopsy samples were subjected to histopathological analysis using transmission electron microscopy and conventional histology. Results Conventional histological analysis revealed subtle abnormalities in the cardiomyocyte morphology of MFS patients, compared to non-MFS and controls. Overall, a slight increase in interstitial fibrosis and mild myocyte hypertrophy were observed in MFS patients. Ultrastructural examination of both MFS and non-MFS patients revealed significant structural remodeling and degenerative changes in the myocardium. These changes included: extensive myofibril lysis, compromised cell membrane integrity and nuclear chromatin condensation. Degenerative lesions were often accompanied by cytoplasmic debris, lysosomal residual bodies, autophagic vacuoles, and severe mitochondrial pathology. Dense accumulation of glycogen granules and lipofuscin was evident in areas of focal myofibril lysis. Notably, only MFS patients exhibited recruitment of granulocytes, including mast cells, eosinophils and neutrophils. A subset of MFS patients displayed advanced stages of myocardial degeneration. However, these changes did not correlate with clinical myocardial failure. Conclusions To the best of our knowledge, this study represents the first evidence of ultrastructural changes in the myocardium of patients with MFS. Our data indicate various degenerative changes in the myocardial architecture, including structural and metabolic myocardial remodeling, along with inflammatory cell infiltration. We believe that our findings of ultrastructural lesions reflect the complexity of myocardial disease in MFS and emphasize the importance of careful surveillance for cardiomyopathy in MFS patients. Further studies are warranted to confirm whether the observed granulocyte influx is specific to MFS and to clarify its role in MFS myocardial disease pathophysiology.Graphical abstract

Clinical outcomes and impact of mitral valve surgery in atrial functional mitral regurgitation: the REVEAL-AFMR registry

Abstract Background The real-world impact and effective treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. The aim of this study was to investigate the prevalence, clinical characteristics, and the effectiveness of mitral valve surgery in AFMR. Methods The REal-world obserVational study for invEstigAting the prevaLence and therapeutic options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR) was a retrospective cohort study conducted across 26 Japanese centers. All transthoracic echocardiography performed in 2019 were reviewed and patients with moderate or severe AFMR defined by preserved left ventricular function, dilated left atrium, and absence of degenerative valvular changes. The primary composite outcomes were heart failure hospitalization and all-cause mortality. Besides traditional multivariable regression analysis, propensity score-based time-zero matching was performed to account for immortal time bias. Results In 177,235 patients who underwent echocardiography, 8,867 had moderate or severe MR. Within this group, 1,007 were diagnosed with AFMR (mean age 78±10, 56% female, 80% atrial fibrillation). Of these, 113 underwent MV surgery, with 81% receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR, larger left heart chambers, and a higher prevalence of heart failure than those who remained under medical therapy. During a median follow-up of 1050 days, 28% experienced the primary outcome, and 18% died. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had significantly lower rate of the primary outcome (hazard ratio 0.43 [0.29-0.64], p&amp;lt;0.001 after adjustment for 25 covariates). Propensity score-based time-zero matching also indicated a lower risk of the primary outcome in the surgical group (hazard ratio 0.39 [0.20–0.78], p=0.007). Multiple sensitivity analyses yielded consistent results. Subgroup analysis suggested a significantly greater benefit of surgery for patients with severe MR than those with non-severe MR (p for interaction=0.044). Conclusions Our registry revealed that patients with AFMR are typically old with predominantly with atrial fibrillation, facing poor outcomes. MV surgery was associated with fewer adverse events, a finding that should be validated in future clinical trials.

Management of Rotator Cuff Injuries: Surgical Repair vs. Conservative Treatment

Rotator cuff injuries are a common cause of shoulder pain and dysfunction, resulting from acute trauma or degenerative changes. These injuries, including partial and full-thickness tears, can significantly impair daily activities and reduce quality of life. Treatment options range from conservative measures, such as physical therapy and NSAIDs, to surgical interventions like arthroscopic repair. The choice of treatment depends on factors such as tear size, patient age, and activity level. This review compares the effectiveness of conservative treatment and surgical repair for rotator cuff injuries, focusing on pain relief, functional recovery, and complication rates. Conservative treatment is typically the first-line approach for partial-thickness tears or patients with lower physical demands. Physical therapy and nonsteroidal anti-inflammatory drugs are common modalities that can improve symptoms, particularly for smaller tears. Corticosteroid injections are also used to provide short-term relief, although their long-term benefits are less clear. For larger or full-thickness tears, surgery is often necessary due to the risk of progressive degeneration and persistent symptoms. Arthroscopic repair is particularly beneficial for younger or more active patients, offering superior long-term outcomes in terms of strength and function. Studies indicate that while conservative treatment and surgery may offer similar short-term outcomes for smaller tears, surgery provides better long-term recovery for more extensive injuries. Ultimately, the decision between conservative and surgical treatment should be individualized, considering tear size, patient age, activity level, and overall health. Surgery is recommended for full-thickness tears or when conservative treatment fails to yield sufficient improvement, while conservative management remains effective for many smaller tears.

Treatment Options for Plantar Fasciitis: Surgical Release vs. Conservative Therapy

Introduction Plantar fasciitis is one of the most common reasons for visits to orthopedic clinics. This tendinopathy can cause medial heel pain, stiffness, and tenderness on the plantar surface of the foot. Both conservative and surgical methods are employed in its treatment. Aim The aim of this study is to evaluate selected conservative treatment methods, such as stretching, the use of orthotic insoles, splints, injections, extracorporeal shockwave therapy, and taping, as well as surgical treatment options. The study presents a comparison of these methods in terms of their effectiveness, advantages, and disadvantages. State of Knowledge The plantar fascia is a stiff, connective tissue structure extending along the plantar surface of the foot. Biomechanical load on the fascia, which supports the medial longitudinal arch, can lead to degenerative changes that underlie plantar fasciitis. Symptoms include pain, particularly in the mornings and late evenings, which intensifies with palpation of the heel area. Summary (Conclusions) Conservative treatments for plantar fasciitis are effective in 90% of patients. There are no studies that conclusively demonstrate the superiority of one treatment method over another. Thus, the choice of therapy should be tailored to the patient's lifestyle, activity level, and financial capability. Surgical intervention is necessary in cases of chronic plantar fasciitis which remains resistant to conservative treatments.

Establishment of rabbit knee osteoarthritis model by simple anterior cruciate ligament disruption

The rabbit knee osteoarthritis(KOA) model was established by simple anterior cruciate ligament disruption. The selected 40 adult white rabbits were randomly divided into two groups, blank group with 6 rabbits and model group with 34 rabbits. The rabbits in model group were given the disruption of anterior cruciate ligament of right knee joint. In the fourth, eighth and the twelfth weeks of modeling, different degrees of degenerative changes have been observed on the rabbits articular cartilages from both macroscopic and microscopic aspects. At 4, 8 and 12 weeks after modeling, the articular cartilage of the rabbits in the model group showed degenerative changes in different degrees. At 8 and 12 weeks, the typical pathological manifestations of KOA in the middle and late stages were found in the infrapatellar fat pad and synovium, respectively. There were no changes in articular cartilage, infrapatellar fat pad and synovial membrane in the blank group at the same time. There were significant differences in the gross score between the model group and the blank group at 4 weeks [(1.300±0.674) vs 0.000], 8 weeks [(2.400±0.516) vs 0.000] and 12 weeks [(3.583±0.668) vs 0.000] (P<0.05), the histopathological scores were significantly different, at 4 weeks [(2.900±0.567) vs 0.000], 8 weeks [(7.500±1.178) vs (0.500±0.707)], 12 weeks[(11.833±1.337) vs (1.500±0.707)], (P<0.05). The establishment of rabbit knee arthritis model by simply cutting the anterior cruciate ligament is simple and feasible, with good stability, high success rate, small trauma, short modeling cycle and less changes in animal physiological structure. The rabbit knee arthritis model established by simply cutting the anterior cruciate ligament has good modeling effect on different stages and grades of knee osteoarthritis, and the postoperative infection and trauma can be controlled, which can meet the test requirements.

A case report on dilated engorged epidural vein causing sciatica

Sciatica is most of the time due to lumbar disc herniation. Some other pathologies such as aneurysmal bone cysts, proximal femur osteomyelitis, arachnoid cysts, facetal cysts, giant cell tumours, and pyriformis syndrome mimic sciatica are termed sciatica mimickers in literature. In this case report, we present a 66-year-old man with low back pain and left sciatica and neurogenic claudication who underwent transforaminal lumbar interbody fusion L4–5. In magnetic resonance imaging, the finding was degenerative changes with foraminal stenosis of L4–L5, but intraoperatively, we found an engorged epidural vein causing the compression of L4 exiting nerve root. The engorged epidural vein sometimes can cause sciatica which mimics the disc herniation.

Therapeutic potential of d-limonene in rheumatoid arthritis: Modulation of inflammatory, anti-inflammatory cytokines, and prostaglandin E2.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d-Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus, and in citrus fruits such as lemon and orange. It has reported anti-inflammatory and anti-nociceptive properties and was selected for the current study as a potential anti-arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant-induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti-arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post-intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor-α, interleukin (IL)-1β, nuclear factor-κB, matrix metalloproteinase-3, IL-6, and IL-4 in the blood. The levels of PGE2 were evaluated by enzyme-linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti-arthritic potential of the compound.

Biomarker and adverse outcome pathway responses of Tubifex tubifex(sludge worm) exposed to environmentally-relevant levels of acenaphthene: insights from behavioral, physiological, and chemical structure-activity analyses.

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure-activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure-activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments.

Corrective Intra-articular Osteotomy for Malreductions of Tibial Pilon Fractures in Patients Less Than 55 Years Old.

Tibial pilon malreductions are challenging to correctively reconstruct, and the relevant literature is limited. This study aims to assess whether corrective intra-articular osteotomy is worthwhile to treat relatively younger (<55-year-old) patients with intra-articular malreductions of pilon fractures. This is a retrospective observational study with a minimum follow-up of 2 years. From 2013 to 2021, 21 patients (mean age: 39.2 ± 11.2 years) with intra-articular pilon malreductions ≥6 weeks treated with intra-articular osteotomies were analyzed. The median interval time until intra-articular osteotomy was 76 (interquartile range [IQR], 49-149) days. Plain radiographs and computed tomography were used for radiographic assessments. Clinical outcomes were evaluated with visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, the 36-Item Short-Form Health Survey (SF-36) score, and ankle range of motion (ROM). The median follow-up duration was 34.6 (IQR, 26.1-74.3) months. The median articular displacement was reduced from 12.7 mm preoperatively to 2.7 mm postoperatively (P < .05). According to the Kellgren-Lawrence grading, 16 patients were assigned to stage II, 4 to stage III, and 1 to stage IV. In the 10 patients with available preoperative assessments, substantial improvement was found in the VAS score, from 5.90 to 2.0 at the final follow-up (P < .05). Similarly, the AOFAS ankle-hindfoot score and SF-36 scores improved (P < .05). Ankle ROM did not change a clinically meaningful amount. Progressive degenerative changes were noted in 2 of 10 patients who had adequate preoperative imaging. Four patients had VAS scores ≥4 including 1 patient who is scheduled for an arthrodesis. In this small series, we found that the corrective osteotomies generally provided reasonable improvement at 3 years in patients <55 years old with intra-articular malreduction of pilon fractures. Prospective cohort studies are needed to determine if it is worthwhile in long-term outcome.

Genetic framework sequencing analysis of Candida tropicalis in dairy cow mastitis and study of pathogenicity and drug resistance

Candida tropicalis (C. tropicalis) is a zoonotic pathogen that is widespread in the environment and in recent years an increasing number of dairy cows have been infected with the fungus causing mastitis in cows.In this study, 37 milk samples from the udders of cows with clinical mastitis were collected from a dairy farm in Guangxi Province, China, from which C. tropicalis was isolated and identified, and then the isolated fungi were subjected to genome frame map sequencing, genome functional analysis as well as comparative genome analysis of the sequencing results, and combined with the virulence test of the fungi and drug sensitivity test of the fungi determined in infected mice, the resistance genes and pathogenicity of the fungi were Analysis of resistance genes and pathogenicity.Our study results revealed the isolation and characterisation of C. tropicalis from diseased cows, with a genome length of approximately 14.27 Mb. Functional annotation of the genome identified 4068 genes associated with C. tropicalis. The strain exhibited a chemoresistance mutation in the gene cyp51,a virulence-enhancing mutation in the gene VTC4, and mutations in genes linked to drug resistance. Pathogenicity tests demonstrated that C. tropicalis could induce damage to the internal organs of mice, leading to different levels of cyanosis in the abdominal cavity, white necrotic foci on the surface of internal organs, lung hemorrhage, and enlargement of the spleen and thymus.Histological sections also revealed varying degrees of hemorrhage and degenerative changes in the cells of different organs in the mice. Drug sensitivity tests showed that the fungus was highly sensitive to nystatin and ketoconazole, moderately sensitive to amphotericin B, and insensitive to antibiotics such as itraconazole, gentamicin, and penicillin. In conclusion, C. tropicalis isolated from dairy cows in the Guangxi region in this study was pathogenic and resistant to azoles such as itraconazole and fluconazole, and this study provides a theoretical basis for the further screening of novel resistance genes in C. tropicalis, as well as providing a certain reference for the drugs used for the treatment of fungal cow mastitis in this region.

Diallyl Disulfide Mitigates Cadmium Hepatotoxicity by Attenuating Oxidative Stress and TLR-4/NF-κB Signaling and Upregulating PPARγ.

Heavy metals can cause serious health problems that affect different organs. Cadmium (Cd) is an environmental contaminant known for its toxicological consequences on different organs. Hepatotoxicity is a serious effect of exposure to Cd with oxidative stress (OS) and inflammation playing a central role. Diallyl disulfide (DADS), an organo-sulfur compound found in garlic, is known for its cytoprotective and antioxidant effects. In this study, the effect of DADS on Cd-induced inflammation, oxidative stress and liver injury was investigated. DADS was supplemented for 14 days via oral gavage, and a single intraperitoneal dose of Cd (1.2 mg/kg body weight) was administered to rats on day 7. Blood and liver samples were collected at the end of the experiment for analyses. Cd administration resulted in remarkable hepatic dysfunction, degenerative changes, necrosis, infiltration of inflammatory cells, collagen deposition and other histopathological alterations. Cd increased liver malondialdehyde (MDA) and nitric oxide (NO) (p < 0.001), upregulated toll-like receptor (TLR)-4, nuclear factor-kappaB (NF-κB), pro-inflammatory mediators, and caspase-3 (p < 0.001) whereas decreased glutathione (GSH) and antioxidant enzymes (p < 0.001). Cd downregulated peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in inflammation and OS suppression (p < 0.001). DADS ameliorated liver injury and tissue alterations, attenuated OS and apoptosis, suppressed TLR-4/NF-κB signaling, and enhanced antioxidants. In addition, DADS upregulated PPARγ in the liver of Cd-administered rats. DADS is effective against Cd-induced hepatotoxicity and its beneficial effects are linked to suppression of inflammation, OS and apoptosis and upregulation of PPARγ. DADS could be valuable to protect the liver in individuals at risk of Cd exposure, pending further studies to elucidate other underlying mechanism(s).

Anti-Inflammatory effect of INSL-3 on experimental arthritis model and LPS-induced macrophage cell line

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that affects the joints of approximately 1 % of the population worldwide and is seen 2–4 times less in males. INSL3 is a gender-specific peptide hormone produced much higher in males than in females and may have an anti-inflammatory role in RA. So, in this study, it was aimed to determine the possible anti-inflammatory effect and dose of insulin-like factor-3(INSL3) in an experimental Complete Freund’s adjuvant(CFA)-induced RA male rat model and lipopolysaccharide(LPS)-induced macrophage cell line and compare it with prednisolone therapy. For in vivo experiments, 48 male mice were randomly divided into 6 groups with 8 subjects in each group: Control group, Arthritis group, Arthritis + Prednisolone(10 mg/kg) group, Arthritis + INSL3(0.08–0.8–8 μg/day) groups. Joint tissue samples obtained from sacrificed subjects were examined by histochemical and immunohistochemically methods after biometric analyses, arthritis severity scoring, and thermal latency experiments. LPS-induced macrophage cells were also treated with prednisolone(1 µg/ml) and INSL3(50–100-200 nM). Cell viability, cell morphology, and TNF-α and IL-6 immune reactivity were evaluated. According to the data obtained from in vivo analyses, it was seen that INSL3 reduced the paw diameter and arthritis severity scoring, degenerative changes, and inflammation and increased the thermal latency, compared to the arthritis group, although not as much as the prednisolone treatment group. In vitro analyses showed that high doses of INSL3 had positive effects on cell viability, morphology, TNF-α, and IL-6 immune reactivity. In conclusion, it was determined that the anti-inflammatory effect of INSL3 was not as pronounced as prednisolone, but it had a more favorable impact on macrophage cell viability and morphology. It was concluded that INSL3 may be a protective therapeutic agent in combination with existing treatment protocols in treating many autoimmune diseases.

Impact of Cyclophosphamide on Testis and Sexual Glands of Adult Albino Rats and Probable Recovery After Drug Withdrawal: A Histological and Immunohistochemical study

Background: Cyclophosphamide is a chemotherapy and an immune-suppressive drug which is used for treatment of malignant and immune –related disease. The current work was conducted to evaluate the histological structure of the male gonad and sexual glands during treatment and after discontinuation of cyclophosphamide. Material and Methods: Thirty male albino- rats were classified into three groups. The first one was treated by normal saline, the second and third groups received cyclophosphamide 150 mg/kg intra peritoneal every two days for one week. The third group regarded as recovery group and divided into two subgroups with one- or two-months’ recovery period. At the accomplishment of the work, blood was drowning for hormonal analysis (testosterone) then the animals were sacrificed. The testis, prostate and seminal vesicle were removed and prepare for histological and immunohistochemical staining. Results: The cyclophosphamide treated group (GII) showed reduction of serum testosterone level, the testicular and sexual glands sections revealed atrophic and degenerative changes of their lining epithelium with reduction of their function and changes of their Ki67 expression which indicate abnormal proliferative pattern of the cells. However, the histopathological changes of treated group showed no improvement after one or even two months of drug withdrawal. Conclusion: The present study pointed out the risk of infertility and gonadal toxicity during cyclophosphamide treatment which may be permanent even after termination of the treatment.