Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes.

Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014.

Emerging role of caldesmon in cancer: A potential biomarker for colorectal cancer and other cancers.

Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon (CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD (l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancer-associated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer.

Estrogen-induced hypomethylation and overexpression of YAP1 facilitate breast cancer cell growth and survival.

Increased expression of Yes-associated protein-1 (YAP1) was shown to correlate with reduced survival in breast cancer (BC) patients. However, the exact mechanism of YAP1 regulation in BC cells remains ambiguous. Genomic sequence search showed that the promoter region of the YAP1 gene contains CpG Islands, hence the likelihood of epigenetic regulation by DNA methylation. To address this possibility, the effect of estrogen (17ß estradiol; E2) on YAP1 gene expression and YAP1 promoter methylation status was evaluated in BC cells. The functional consequences of E2 treatment in control and YAP1-silenced BC cells were also investigated. Our data showed that E2 modulates YAP1 expression by hypomethylation of its promoter region via downregulation of DNA methyltransferase 3B (DNMT3B); an effect that seems to facilitate tumor progression in BC cells. Although the effect of E2 on YAP1 expression was estrogen receptor (ER) dependent, E2 treatment also upregulated YAP1 expression in MDA-MB231 and SKBR3 cells, which are known ER-negative BC cell lines but expresses ERα. Functionally, E2 treatment resulted in increased cell proliferation, decreased apoptosis, cell cycle arrest, and autophagic flux in MCF7 cells. The knockdown of the YAP1 gene reversed these carcinogenic effects of E2 and inhibited E2-induced autophagy. Lastly, we showed that YAP1 is highly expressed and hypomethylated in human BC tissues and that increased YAP1 expression correlates negatively with DNMT3B expression but strongly associated with ER expression. Our data provide the basis for considering screening of YAP1 expression and its promoter methylation status in the diagnosis and prognosis of BC.

Functional beta-cells derived from umbilical cord blood mesenchymal stem cells for curing rats with streptozotocin-induced diabetes mellitus.

INTRODUCTION: This study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus. METHODS: Control group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue. RESULTS: Haematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin. CONCLUSION: UCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats.

Autophagy related markers (Beclin-1 and ATG4B) are strongly expressed in Wilms' tumor and correlate with favorable histology.

BACKGROUND: Wilms' tumor treatment has achieved great success in the last decade. Nevertheless, some cases still fail to respond to the current multimodality therapy. These cases fall mainly in the unfavorable histology group with very few belonging to the favorable histology group. In recent years, autophagy manipulation whether inhibition or stimulation has been shown to affect cancer cell behavior and has emerged as a novel mechanism to improve cancer cell response to currently used therapeutic regimens. OBJECTIVE: The current study aimed to investigate the expression of autophagy related markers (ATG4B and Beclin1) in WT, its association with the different clinic-pathological parameters and its impact on patient survival. METHODS: Twenty-one formalin fixed paraffin embedded (FFPE) WT specimens were immunohistochemically stained using autophagy related markers; Beclin-1 and ATG4B. All clinical, radiological and follow up data were retrieved from the patient records. RESULTS: All specimens showed positive expression of both Beclin-1 and ATG4B. The staining score for Beclin1 varied between 50 and 300, and its expression was significantly associated with favorable histology (p=0.007). Similarly, ATG4B expression was significantly higher in favorable histology tumors compared to unfavorable histology (p=0.046). A statistically significant positive correlation between Beclin-1 and ATG4B expression was observed. The cumulative disease-free survival in patients with favorable histology was significantly higher compared to patients with unfavorable histology (p=0.0027). CONCLUSIONS: Beclin-1 and ATG4B expression were both found to be statistically significant discriminators of survival. Collectively these findings suggest that the expression of autophagy-related markers is associated with a favorable histology and could predict better survival in these patients.

Prevalence and pattern of dokha use among medical and allied health students in Ajman, United Arab Emirates.

Globally, tobacco is considered to be one among the leading causes of death. Dokha is a mixture of Iranian tobacco with aromatic leaf and bark herbs, smoked in a small pipe termed a Midwakh thought to have originated in the Arabian Peninsula. The present study aimed at evaluating the prevalence and pattern of dokha use among Medical University students. Prior to participation in the study, the students were provided with information on the purpose of the study and also assured that confidentiality would be maintained. A self-administered questionnaire was then utilized for collection of data which were processed using Excel spread sheet and analysed using PASW 17. A total of 104 students between 17 and 27 years of age participated, 75% of the respondents being females. The prevalence of dokha smoking was higher among male participants than females. Among dokha smokers, the majority (18.6%) were from the College of Allied Health Sciences. 11.5% reported as being lifetime smokers of dokha and 25% had smoked dokha daily over the past month. We conclude that dokha use among our target population is common and hence favor developmentn of an anti-smoking program for university students.

Extensor carpi radialis brevis origin, nerve supply and its role in lateral epicondylitis.

Lateral epicondylitis (LE) or tennis elbow has been the subject of concern during the last 60 years, but the pathogenesis of the LE remains unclear. The LE can be due to the tendinogenic, articular or neurogenic reasons. Numerous theories have been put fourth in the recent past, out of which one of the most popular theories is that the condition results from repeated contraction of the wrist extensor muscles, especially the extensor carpi radialis brevis (ECRB) which may compress the posterior branch of the radial nerve (PBRN) at the elbow during pronation. We studied 72 upper limbs (36 formalin-fixed cadaver) for the origin, nerve supply and the course of PBRN in relation to the ECRB as one of the goal for the present study. The possible presence of an arch of the ECRB around the PBRN was also observed and recorded. The nerve to ECRB was a branch from the radial nerve in 11 cases (15.2%); from the PBRN in 36 cases (50%) and from the superficial branch of the radial nerve in 25 cases (34.7%), respectively. The ECRB had a tendinous arch in 21 cases (29.1%); a muscular arch in 8 (11.1%) cases and the arch was absent in 43 cases (59.7%). When the ECRB had a tendinous or muscular arch around the PBRN, it may compress the same and this condition may worsen during the repeated supination and pronation as observed in tennis and cricket players. The presence of such tendinous or muscular arch should be considered by orthopedicians and neurosurgeons, while releasing the PBRN during LE surgery.

Palmar type of median artery as a source of superficial palmar arch: a cadaveric study with its clinical significance.

The superficial palmar arch (SPA) and its contributing arteries are highly variable. The palmar type of median artery (PMA) can be involved in the formation of the SPA by replacing the superficial palmar branch of the radial artery (RA) or the ulnar artery (UA). The present study was undertaken to investigate the presence of the PMA and its contribution in the formation of SPA in 42 cadavers (84 upper limbs) of Indian origin. When there was a PMA, its outer diameter was measured in the carpal tunnel. The PMA was found in 13 upper limbs (15.4%), and of these ten incidences (11.9%), the PMA took part in the formation of SPA, and in three instances (3.5%), the PMA did not make up part of the SPA. Out of the ten cases in which the PMA contributed to the formation of SPA, in six cases (7.1%), the PMA anastomosed with the UA; in three cases (3.5%), the PMA anastomosed with both the UA and the RA, and in one incidence (1.1%), the PMA joined the arteria radialis indicis (deep branch of the RA) to complete the SPA. The outer diameters of the median arteries varied between 0.8 and 2.6 mm with the mean value of 1.7 mm. The present study concludes that the median-ulnar type of SPA was the most common type of SPA when the PMA was encountered as a source of superficial arterial arcade of the hand, followed by the radial-median-ulnar type. The vascular patterns found in this study are important to hand surgeons. The present study of PMA origin, course, and its contribution to the SPA will add to the existing knowledge of the vascular anatomy of forearm and hand.

The nasal septum: an osteometric study of 16 cadaver specimens.

Studies of the shape, dimensions, and other morphologic characteristics of the nasal septum are scant in the literature. We conducted a study of 16 male cadavers to measure six osseous components of the nasal septum and to calculate the proportional contribution that each made to the total septal bone surface area. We found a wide range of inter-specimen variations in both categories. It is our hope that a better understanding of nasoseptal anatomy will improve surgical technique.

Multiple variations of extensor muscles of forearm in relation to the radial nerve: a case report and review / Múltiples variaciones de los músculos extensores del antebrazo en relación con el nervio radial: reporte de caso y revisión

During routine dissection in the Department of Anatomy, multiple variations of forearm muscles in relation to the radial nerve and its branches were observed on the right side of a 34 year old male cadaver. Brachioradialis close to its origin was receiving muscle fibers from the brachialis and the radial nerve was passing in between them. Extensor carpi radialis brevis was absent and the extensor carpi radialis longus was giving two tendons in the second compartment of extensor retinaculum before its insertion while passing deep to the abductor pollicis longus. Absence of extensor carpi radialis brevis can be explained with the arrangement in lower mammals, where the two extensores carpi radiales are represented by one muscle. Ontogeny repeats phylogeny and anatomical variations have developmental basis. Henee, the pattern of muscular arrangement in this case can be said to be less evolved than the usual arrangement. The course of radial nerve between the two heads of brachioradialis makes it highly vulnerable to compression and injury, which may manifest as wrist drop (radial nerve palsy) or radial tunnel syndrome (compression of posterior interosseous nerve).

Durante una disección de rutina en el Departamento de Anatomía, se observaron múltiples variaciones de los músculos del antebrazo, en relación con el nervio radial y sus ramos, en el lado derecho de un cadáver de 34 años de edad, de sexo masculino. Cerca de su origen el músculo braquioradial recibía fibras del músculo braquial y el nervio radial cruzaba entre ellos. El músculo extensor radial corto del carpo se encontraba ausente y el músculo extensor radial largo del carpo se continuaba con dos tendones en el segundo compartimiento del retináculo extensor, bajo el músculo abductor largo de pulgar, antes de su inserción. La ausencia del músculo extensor radial corto del carpo se puede explicar en mamíferos inferiores, donde los dos músculos extensores radiales están representados por un sólo músculo. La ontogenia repite la filogenia y las variaciones anatómicas inciden en su desarrollo. Por lo tanto, de acuerdo al patrón muscular se puede afirmar que en este caso existe menos evolución que lo habitual. El curso del nervio radial entre las dos cabezas del músculo braquioradial, lo hace muy vulnerable a la compresión y las lesiones, que pueden manifestarse son, caída de la muñeca (parálisis del nervio radial) o el síndrome del túnel radial (compresión del nervio interóseo posterior).

Anatomical variation of radial wrist extensor muscles: a study in cadavers.

OBJECTIVE: The tendons of the extensor carpi radialis longus and brevis muscles are quite useful in tendon transfer, such as in correction of finger clawing and restoration of thumb opposition. Knowledge of additional radial wrist extensor muscle bellies with independent tendons is useful in the above-mentioned surgical procedures. METHODS: The skin, subcutaneous tissue, and antebrachial fascia of 48 (24 on the right side and 24 on left side) male upper limb forearms were dissected. The following aspects were then analyzed: (a) the presence of additional muscle bellies of radial wrist extensors, (b) the origin and insertion of the additional muscle, and (c) measurements of the muscle bellies and their tendons. RESULTS: Five out of 48 upper limbs (10.41%) had additional radial wrist extensors; this occurred in 3 out of 24 left upper limbs (12.5%) and 2 out of 24 right upper limbs (8.3%). In one of the right upper limbs, two additional muscles were found. The length and width of each additional muscle belly and its tendon ranged between 2 - 15 cm by 0.35 - 6.4 cm and 2.8 - 20.8 cm by 0.2 0.5 cm, respectively. The additional radial wrist extensor tendons in our study basically originated either from the extensor carpi radialis longus or brevis muscles and were inserted at the base of the 2nd or 3rd metacarpal bone. CONCLUSION: The present study will inform surgeons about the different varieties of additional radial wrist extensors and the frequency of their occurrence.

Anatomical variation of radial wrist extensor muscles: a study in cadavers

OBJECTIVE: The tendons of the extensor carpi radialis longus and brevis muscles are quite useful in tendon transfer, such as in correction of finger clawing and restoration of thumb opposition. Knowledge of additional radial wrist extensor muscle bellies with independent tendons is useful in the above-mentioned surgical procedures. METHODS: The skin, subcutaneous tissue, and antebrachial fascia of 48 (24 on the right side and 24 on left side) male upper limb forearms were dissected. The following aspects were then analyzed: (a) the presence of additional muscle bellies of radial wrist extensors, (b) the origin and insertion of the additional muscle, and (c) measurements of the muscle bellies and their tendons. RESULTS: Five out of 48 upper limbs (10.41 percent) had additional radial wrist extensors; this occurred in 3 out of 24 left upper limbs (12.5 percent) and 2 out of 24 right upper limbs (8.3 percent). In one of the right upper limbs, two additional muscles were found. The length and width of each additional muscle belly and its tendon ranged between 2 - 15cm by 0.35 - 6.4cm and 2.8 - 20.8cm by 0.2 0.5cm, respectively. The additional radial wrist extensor tendons in our study basically originated either from the extensor carpi radialis longus or brevis muscles and were inserted at the base of the 2nd or 3rd metacarpal bone. CONCLUSION: The present study will inform surgeons about the different varieties of additional radial wrist extensors and the frequency of their occurrence.

Estudio piloto del ángulo y rama de la mandíbula en la población hindú / A pilot study of the mandibular angle and ramus in indian population

To evaluate the mandibular angle and to analyze the relationship of the angle and height & breadth of the ramus of the mandible to the gender, so as to study its role in the anthropological diagnosis. The angle, height and breadth of the ramus of adult dry human mandibles of both sexes were measured using a goniometer. The values obtained were analyzed statistically. The present study showed a statistically significant difference in the mandibular angle as well as height of the ramus between both the sexes. The mean mandibular angle of Indian population when compared to that of European population was found to be lower by 9 degrees. The findings of this study might be useful in providing anthropological data that can also be used in dental and medical practice. However, the Indian mandible can be used for sexual dimorphism as is usual in anthropological work; it appears to possess important unfavourable anatomic factors that may predispose the individuals to difficult laryngoscopy or intubation.

Para estudiar su rol en el diagnóstico antropológico, evaluamos el ángulo de la mandíbula y analizamos las relaciones de este ángulo con la altura y ancho de la rama de la mandíbula, en ambos sexos. Con un goniómetro, en huesos secos, fue obtenido el ángulo, alto y ancho de las mandíbulas humanas. Los valores obtenidos fueron analizados estadísticamente. El estudio mostró diferencias estadísticamente significativas en el ángulo mandibular como también en la altura de la rama de la mandíbula, en ambos sexos. La media del ángulo mandibular de la población hindú fue 9 grados menor, comparada con la población europea. Los resultados de este estudio pueden ser útiles al aportar datos antropológicos utilizados en las prácticas médica y dental. Por otra parte, la mandíbula de los hindúes puede ser usada como dimorfismo sexual como es usual en trabajos antropológicos. Parece haber factores anatómicos desfavorabes importantes que pueden predisponer a los individuos a laringoscopías difíciles o intubación.

An additional radial wrist extensor and its clinical significance.

The knowledge of anatomical variations in the antebrachial and dorsal regions of the arm and hand are useful in hand surgery. The extensor carpi radialis intermedius and extensor carpi radialis accessorius are two classic variants described for the radial wrist extensors, in the antebrachial region. We report an additional extensor carpi radialis muscle taking origin from the common extensor origin, between the extensor carpi radialis longus and extensor digitorum communis. The tendon of the variant muscle divides below the abductor pollicis longus and becomes attached to the base of the second and third metacarpal bone. Due to its considerable size and independent origin from the lateral epicondyle, we suggest the present variation should be named extensor carpi radialis tertius. The clinical significance of the present variation is discussed.

Morphometric Study on the Tibial Collateral Ligament / Estudio Morfométrico del Ligamento Colateral Tibial

Tibial collateral ligament by virtue of its length, composite attachments, and biomechanical exertions is more prone to lesions. A systematic analysis of the dimensions and variations of this ligament has been presented in this article. With the decrease emphasis on anatomy as a preclinical subject and recent successful moves to curtail total teaching hours for dissection, coupled with the increasing shortage of cadavers, data of this nature will in our opinion becomes scarce progressively. With these factors in context, and attempt is made to record the gross morphological features of the ligament from a series of dissections.

El ligamento colateral tibial, por virtud de su longitud, inserciones y esfuerzos biomecánicos, está más propenso a lesiones. Un análisis sistemático de las dimensiones y variaciones de este ligamento se presentan en este artículo. El decrecimiento del énfasis de la Anatomía como un ramo preclínico y la falta de cadáveres nos movieron a disminuir las horas de disección. Así, en nuestra opinión, los datos anatómicos son progresivamente más escasos. Con el propósito de registrar las características morfológicas macroscópicas del ligamento colateral tibial, realizamos una serie de disecciones.